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The Nucleolar Aspect of Breast Cancer

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Proteins of the Nucleolus

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Abstract

The oncogenic process of breast cancer is associated with significant morphological and metabolic changes. One aspect of these changes occur in the nucleolus. The nucleolus is the major structure of the nucleus and is responsible for ribosome biosynthesis. Production of pre-rRNA is mediated by RNA polymerase I (Pol I). Pol I-mediated transcription of approximately 200 copies of transcriptionally active rDNA repeats constitutes approximately 60% of nuclear transcription activity. Therefore, the rate of ribosome synthesis in the nucleoli dictates cell proliferation. The upregulation of cell proliferation is a vital aspect of tumorigenesis, including mammary tumorigenesis. While breast cancer forms a group of heterogeneous diseases that are associated with different clinical outcomes, high proliferation rate predicts poor prognosis for all subtypes of breast cancers. In agreement with the above concepts, abnormalities in the number, size, and morphology of nucleoli are generally associated with breast cancer initiation and progression. Furthermore, factors and/or pathways, i.e. tumour suppressors and oncogenes, which regulate mammary tumorigenesis also takes control of ribosome biosynthesis in the nucleoli. In this chapter we will summarize the current understanding of the relationship between nucleoli and breast tumorigenesis.

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References

  • Ahmad Y et al (2009) NOPdb: nucleolar proteome database-2008 update. Nucleic Acids Res 37:D181–D184

    Article  PubMed  CAS  Google Scholar 

  • Arabi A et al (2005) c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nat Cell Biol 7:303–310

    Article  PubMed  CAS  Google Scholar 

  • Aubele M et al (1994) Prognostic value of quantitatively measured AgNORs in ductal mammary carcinoma. Anal Quant Cytol Histol 16:211–218

    PubMed  CAS  Google Scholar 

  • Ayrault O et al (2006) Human tumor suppressor p14ARF negatively regulates rRNA transcription and inhibits UBF1 transcription factor phosphorylation. Oncogene 25:7577–7586

    Article  PubMed  CAS  Google Scholar 

  • Baker S (2007) PTEN enters the nuclear age. Cell 128:25–28

    Article  PubMed  CAS  Google Scholar 

  • Bankfalvi A et al (1998) Relationship between AgNOR proteins, Ki-67 antigen, p53 immunophenotype and differentiation markers in archival breast carcinomas. Anal Cell Pathol 17:231–242

    PubMed  CAS  Google Scholar 

  • Bankfalvi A et al (1999) Standardized in situ AgNOR analysis in breast pathology: diagnostic and cell kinetic implications. Pathol Res Pract 195:219–229

    Article  Google Scholar 

  • Bánkfalvi A et al (2003) Relationship between HER2 status and proliferation rate in breast cancer assessed by immunohistochemistry, fluorescence in situ hybridisation and standardised AgNOR analysis. Int J Oncol 23:1285–1292

    PubMed  Google Scholar 

  • Bantis A et al (2004) Expression of p120, Ki-67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value. Cytopathology 15:25–31

    Article  PubMed  CAS  Google Scholar 

  • Bartova E et al (2010) Structure and epigenetics of nucleoli in comparison with non-nucleolar compartments. J Histochem Cytochem 58:391–403

    Article  PubMed  CAS  Google Scholar 

  • Basu A et al (1997) A comparative study of silver binding nucleolar organiser regions (AgNORs) of breast lesions in histological sections and fine needle aspiration smears. J Indian Med Assoc 95:443–447

    PubMed  CAS  Google Scholar 

  • Baynes C et al (2007) Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk. Breast cancer study. Breast Cancer Res 9:R27

    Article  PubMed  CAS  Google Scholar 

  • Bedard PL et al (2009) Stemming resistance to HER-2 targeted therapy. J Mammary Gland Biol Neoplasia 14:55–66

    Article  PubMed  Google Scholar 

  • Benson JR et al (2009) Early breast cancer. Lancet 373:1463–1479

    Article  PubMed  Google Scholar 

  • Berns K et al (2007) A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12:395–402

    Article  PubMed  CAS  Google Scholar 

  • Bertos NR, Park M (2011) Breast cancer – one term, many entities? J Clin Invest 121:3789–3796

    Article  PubMed  CAS  Google Scholar 

  • Bertwistle D et al (2004) Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin/B23. Mol Cell Biol 24:985–996

    Article  PubMed  CAS  Google Scholar 

  • Biesterfeld S et al (2001) Improvement of breast cancer prognostication using cell kinetic-based silver-stainable nucleolar organizer region quantification of the MIB-1 positive tumor cell compartment. Virchows Arch 438:478–484

    Article  PubMed  CAS  Google Scholar 

  • Blumenthal GM, Dennis PA (2008) PTEN hamartoma tumor syndromes. Eur J Hum Genet 16:1289–1300

    Article  PubMed  CAS  Google Scholar 

  • Bocker T et al (1995) In vitro and ex vivo expression of nucleolar proteins B23 and p120 in benign and malignant epithelial lesions of the prostate. Mod Pathol 8:226–231

    PubMed  CAS  Google Scholar 

  • Bodem G et al (2000) TIF-IA, the factor mediating growth-dependent control of ribosomal RNA synthesis, is the mammalian homolog of yeast Rrn3p. EMBO Rep 1:171–175

    Article  PubMed  CAS  Google Scholar 

  • Boon K et al (2003) Comparison of medulloblastoma and normal neural transcriptomes identifies a restricted set of activated genes. Oncogene 22:7687–7694

    Article  PubMed  CAS  Google Scholar 

  • Borg A et al (1992) The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression. Cancer Res 52:2991–2994

    PubMed  CAS  Google Scholar 

  • Bos PD et al (2009) Genes that mediate breast cancer metastasis to the brain. Nature 459:1005–1009

    Article  PubMed  CAS  Google Scholar 

  • Bosco EE, Knudsen ES (2007) RB in breast cancer: at the crossroads of tumorigenesis and treatment. Cell Cycle 6:667–671

    Article  PubMed  CAS  Google Scholar 

  • Bosco EE et al (2007) The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J Clin Invest 117:218–228

    Article  PubMed  CAS  Google Scholar 

  • Boulon S et al (2010) The nucleolus under stress. Mol Cell 40:216–227

    Article  PubMed  CAS  Google Scholar 

  • Boyd MT et al (2011) The nucleolus directly regulates p53 export and degradation. J Cell Biol 194:689–703

    Article  PubMed  CAS  Google Scholar 

  • Buckley MF et al (1993) Expression and amplification of cyclin genes in human breast cancer. Oncogene 8:2127–2133

    PubMed  CAS  Google Scholar 

  • Budde and Grummt (1999) p53 represses ribosomal gene transcription. Oncogene 18:1119–1124

    Article  PubMed  CAS  Google Scholar 

  • Burkhart DL, Sage J (2008) Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cancer 8:671–682

    Article  PubMed  CAS  Google Scholar 

  • Burness ML et al (2010) Epidermal growth factor receptor in triple-negative and basal-like breast cancer: promising clinical target or only a marker? Cancer J 16:23–32

    Article  PubMed  CAS  Google Scholar 

  • Burney TL et al (1994) Partial growth suppression of human prostate cancer cells by the Krev-1 suppressor gene. Prostate 25:177–188

    Article  PubMed  CAS  Google Scholar 

  • Campeau PM et al (2008) Hereditary breast cancer: new genetic developments, new therapeutic avenues. Hum Genet 124:31–42

    Article  PubMed  CAS  Google Scholar 

  • Canepa M et al (1990) Nucleolar organizer regions and Ki-67 immunostaining in ductal breast cancer: a comparative study. Pathologica 82:125–132

    PubMed  CAS  Google Scholar 

  • Canepa M et al (1993) Nucleolar organizer regions: a prognostic factor in infiltrating ductal carcinoma in the breast. Pathologica 85:151–162

    PubMed  CAS  Google Scholar 

  • Cangi MG et al (2000) Role of the Cdc25A phosphatase in human breast cancer. J Clin Invest 106:753–761

    Article  PubMed  CAS  Google Scholar 

  • Cao X et al (2010) RACK1: a superior independent predictor for poor clinical outcome in breast cancer. Int J Cancer 127:1172–1179

    Article  PubMed  CAS  Google Scholar 

  • Carey LA et al (2006) Race, breast cancer subtypes, and survival in the carolina breast cancer study. JAMA 295:2492–2502

    Article  PubMed  CAS  Google Scholar 

  • Cavanaugh AH et al (1995) Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product. Nature 374:177–180

    Article  PubMed  CAS  Google Scholar 

  • Ceccarelli C et al (1998) Retinoblastoma (RB1) gene product expression in breast carcinoma. Correlation with Ki-67 growth fraction and biopathological profile. J Clin Pathol 51:818–824

    Article  PubMed  CAS  Google Scholar 

  • Ceccarelli C et al (2000) AgNORs in breast tumours. Micron 31:143–149

    Article  PubMed  CAS  Google Scholar 

  • Chambon M et al (2003) Localization of BRCA1 protein in human breast cancer cells. Breast Cancer Res Treat 79:107–119

    Article  PubMed  CAS  Google Scholar 

  • Charrasse S et al (1995) Characterization of the cDNA and pattern of expression of a new gene over-expressed in human hepatomas and colonic tumors. Eur J Biochem 234:406–413

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Olopade OI (2008) MYC in breast tumor progression. Expert Rev Anticancer Ther 8:1689–1698

    Article  PubMed  CAS  Google Scholar 

  • Chen D et al (2010) Identification of prohibitin as a potential biomarker for colorectal carcinoma based on proteomics technology. Int J Oncol 37:355–365

    PubMed  CAS  Google Scholar 

  • Ciarmatori S et al (2001) Overlapping functions of the pRb family in the regulation of rRNA synthesis. Mol Cell Biol 21:5806–5814

    Article  PubMed  CAS  Google Scholar 

  • Colombo E et al (2011) Nucleophosmin and its complex network: a possible therapeutic target in hematological diseases. Oncogene 30:2595–2609

    Article  PubMed  CAS  Google Scholar 

  • Cox LA et al (1994) Tumor suppressor genes and their roles in breast cancer. Breast Cancer Res Treat 32:19–38

    Article  PubMed  CAS  Google Scholar 

  • D’Cruz CM et al (2001) c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 7:235–239

    Article  PubMed  Google Scholar 

  • Dai MS, Lu H (2004) Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5. J Biol Chem 279:44475–44482

    Article  PubMed  CAS  Google Scholar 

  • Dang CV et al (2006) The c-Myc target gene network. Semin Cancer Biol 16:253–264

    Article  PubMed  CAS  Google Scholar 

  • Dell Orco RT et al (1997) Prohibitin: a new biomarker for breast tumors. Breast J 3:85–89

    Article  Google Scholar 

  • Deming SL et al (2000) C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance. Br J Cancer 83:1688–1695

    Article  PubMed  CAS  Google Scholar 

  • Derenzini M (2000) The AgNORs. Micron 31:117–120

    Article  PubMed  CAS  Google Scholar 

  • Derenzini M et al (1990) Diagnostic value of silver-stained interphasic nucleolar organizer regions in breast tumors. Ultrastruct Pathol 14:233–245

    Article  PubMed  CAS  Google Scholar 

  • Derenzini M et al (1992) Relationship between interphase AgNOR distribution and nucleolar size in cancer cells. Histochem J 24:951–956

    Article  PubMed  CAS  Google Scholar 

  • Derenzini M et al (1998) Nucleolar function and size in cancer cells. Am J Pathol 152:1291–1297

    PubMed  CAS  Google Scholar 

  • Derenzini M et al (2009) What the nucleolus says to a tumour pathologist. Histopathology 54:753–762

    Article  PubMed  Google Scholar 

  • Dervan PA et al (1989) Breast carcinoma kinetics. Argyrophilic nucleolar organizer region counts correlate with Ki67 scores. Am J Clin Pathol 92:401–407

    PubMed  CAS  Google Scholar 

  • Di Stefano D et al (1991) A comparative study of histopathology, hormone receptors, peanut lectin binding, Ki-67 immunostaining, and nucleolar organizer region-associated proteins in human breast cancer. Cancer 67:463–471

    Article  PubMed  Google Scholar 

  • Dominguez G et al (2003) Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors. Mutat Res 530:9–17

    Article  PubMed  CAS  Google Scholar 

  • Donnellan and Chetty (1999) Cyclin E in human cancers. FASEB 13:773–780

    CAS  Google Scholar 

  • Dourdin N et al (2008) Phosphatase and tensin homologue deleted on chromosome 10 deficiency accelerates tumor induction in a mouse model of ErbB-2 mammary tumorigenesis. Cancer Res 68:2122–2131

    Article  PubMed  CAS  Google Scholar 

  • Downward J (2003) Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3:11–22

    Article  PubMed  CAS  Google Scholar 

  • Egidy G et al (2008) Transcription analysis is the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation. Mol Cancer 7:34

    Article  PubMed  CAS  Google Scholar 

  • Emmott E, Hiscox JA (2009) Nucleolar targeting: the hub of the matter. EMBO Rep 10:231–238

    Article  PubMed  CAS  Google Scholar 

  • Epping MT et al (2008) PRAME expression and clinical outcome of breast cancer. Br J Cancer 99:398–403

    Article  PubMed  CAS  Google Scholar 

  • Eskelinen MJ et al (1991) The role of nucleolar organiser regions as prognostic factors in breast cancer. Eur J Cancer 27:989–992

    Article  PubMed  CAS  Google Scholar 

  • Falini B et al (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352:254–266

    Article  PubMed  CAS  Google Scholar 

  • Faratian D et al (2009) Systems biology reveals new strategies for personalizing cancer medicine and confirms the role of PTEN in resistance to trastuzumab. Cancer Res 69:6713–6720

    Article  PubMed  CAS  Google Scholar 

  • Foley J et al (2010) EGFR signaling in breast cancer: bad to the bone. Semin Cell Dev Biol 21:951–960

    Article  PubMed  CAS  Google Scholar 

  • Ford D, Easton DF (1995) The genetics of breast and ovarian cancer. Br J Cancer 72:805–812

    Article  PubMed  CAS  Google Scholar 

  • Freeman JW et al (1991) Prognostic significance of proliferation associated nucleolar antigen p120 in human breast carcinoma. Cancer Res 51:1973–1978

    PubMed  CAS  Google Scholar 

  • Fujita T et al (2006) Shimizu N. PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer. Br J Cancer 94:247–252

    Article  PubMed  CAS  Google Scholar 

  • Gaedcke J et al (2007) Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol 20:864–870

    Article  PubMed  CAS  Google Scholar 

  • Gao L et al (2006) Ras-associated protein-1 regulates extracellular signal regulated kinase activation and migration in melanoma cells: two processes important to melanoma tumorigenesis and metastasis. Cancer Res 66:7880–7888

    Article  PubMed  CAS  Google Scholar 

  • Gibson L et al (2009) Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev 4:CD003370

    PubMed  Google Scholar 

  • Gillett C et al (1994) Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res 54:1812–1817

    PubMed  CAS  Google Scholar 

  • Grandori C et al (2005) c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol 7:311–318

    Article  PubMed  CAS  Google Scholar 

  • Grinstein E et al (2002) Nucleolin as activator of human papillomavirus Type 18 oncogene transcription in cervical cancer. J Exp Med 196:1067–1078

    Article  PubMed  CAS  Google Scholar 

  • Grummt I (1999) Regulation of mammalian ribosomal gene transcription by RNA polymerase I. Prog Nucleic Acid Res Mol Biol 62:109–154

    Article  PubMed  CAS  Google Scholar 

  • Grummt I (2003) Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17:1691–1702

    Article  PubMed  CAS  Google Scholar 

  • Grummt I, Ladurner AG (2008) A metabolic throttle regulates the epigenetic state of rDNA. Cell 133:577–580

    Article  PubMed  CAS  Google Scholar 

  • Gunther L et al (2000) Different proliferation patterns in breast cancer: AgNOR measurements in ER-negative and ER-positive tumor cells. Anal Cell Pathol 20:155–162

    PubMed  CAS  Google Scholar 

  • Gushima M et al (2010) Raloxifene induces nucleolar translocation of the estrogen receptor. Mol Cell Endocrinol 319:14–22

    Article  PubMed  CAS  Google Scholar 

  • Hannan KM et al (2000a) Rb and p130 regulate RNA polymerase I transcription: Rb disrupts the interaction between UBF and SL-1. Oncogene 19:4988–4999

    Article  PubMed  CAS  Google Scholar 

  • Hannan KM et al (2000b) RNA polymerase I transcription in confluent cells: Rb downregulates rDNA transcription during confluence-induced cell cycle arrest. Oncogene 19:3487–3497

    Article  PubMed  CAS  Google Scholar 

  • Hasselblom S et al (2008) Low rather than high ki-67 protein expression is an adverse prognostic factor in diffuse large B-cell lymphoma. Leuk Lymphoma 49:1501–1509

    Article  PubMed  CAS  Google Scholar 

  • He L et al (2008) Interaction of p14ARF with Brca1 in cancer cell lines and primary breast cancer. Cell Biol Int 32:1302–1309

    Article  PubMed  CAS  Google Scholar 

  • He J et al (2011) KDM2b/JHDM1b, an H3K36me2-specific demethylase is required for initiation and maintenance of acute myeloid leukemia. Blood 177:3869–3880

    Article  CAS  Google Scholar 

  • Hehir DJ et al (1992) Argyrophylic nucleolar organiser regions (AgNOR’s) as a prognostic indicator in breast carcinoma. Ir J Med Sci 161:112–115

    Article  PubMed  CAS  Google Scholar 

  • Heiss NS et al (1998) X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 19:32–38

    Article  PubMed  CAS  Google Scholar 

  • Hernandez N (1993) TBP, a universal eukaryotic transcription factor? Genes Dev 7:1291–1308

    Article  PubMed  CAS  Google Scholar 

  • Hernandez-Verdun D (1991) The nucleolus today. J Cell Sci 99(Pt 3):465–471

    PubMed  Google Scholar 

  • Herschkowitz JI et al (2008) The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas. Breast Cancer Res 10:R75

    Article  PubMed  CAS  Google Scholar 

  • Hicks DG et al (2006) Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR. Am J Surg Pathol 30:1097–1104

    Article  PubMed  Google Scholar 

  • Higgins and Baselga (2011) Targeted therapies for breast cancer. J Clin Invest 121:3797–3803

    Article  PubMed  CAS  Google Scholar 

  • Hortobagyi GN et al (2005) ABREAST Investigators. The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer 6:391–401

    Article  PubMed  Google Scholar 

  • Htun H et al (1999) Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor. Mol Biol Cell 10:471–486

    PubMed  CAS  Google Scholar 

  • Hu J et al (2011) DIGE-based proteomic analysis identifies nucleophosmin/B23 and nucleolin C23 as overexpressed proteins in relapsed/refractory acute leukemia. Leuk Res 35:1087–1092

    Article  PubMed  CAS  Google Scholar 

  • Huang M et al (2011) Cyclopentenyl cytosine induces senescence in breast cancer cells through the nucleolar stress response and activation of p53. Mol Pharmacol 80:40–48

    Article  PubMed  CAS  Google Scholar 

  • Hutchinson JN, Muller WJ (2000) Transgenic mouse models of human breast cancer. Oncogene 19:6130–6137

    Article  PubMed  CAS  Google Scholar 

  • Hynes NE, Stoelzle T (2009) Key signalling nodes in mammary gland development and cancer: Myc. Breast Cancer Res 11:210

    Article  PubMed  CAS  Google Scholar 

  • Ikeda H et al (1997) Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6:199–208

    Article  PubMed  CAS  Google Scholar 

  • Ilan N et al (2006) Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. Int J Biochem Cell Biol 38:2018–2039

    Article  PubMed  CAS  Google Scholar 

  • Itahana K et al (2003) Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation. Mol Cell 12:1151–1164

    Article  PubMed  CAS  Google Scholar 

  • Jares P et al (1997) Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status. J Pathol 182:160–166

    Article  PubMed  CAS  Google Scholar 

  • Ji D et al (2007) A screen of shRNAs targeting tumour suppressor genes to identify factors involved in A549 paclitaxel sensitivity. Oncol Rep 18:1499–1505

    PubMed  CAS  Google Scholar 

  • Jiang Z et al (2010) Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. J Clin Invest 120:3296–3309

    Article  PubMed  CAS  Google Scholar 

  • Jirstrom K et al (2005) Adverse effect of adjuvant tamoxifen in premenopausal breast cancer with cyclin D1 gene amplification. Cancer Res 65:8009–8016

    PubMed  Google Scholar 

  • Jordan VC (2008) The 38th David A. Karnofsky lecture: the paradoxical actions of estrogen in breast cancer–survival or death? J Clin Oncol 26:3073–3082

    Article  PubMed  CAS  Google Scholar 

  • Kang X et al (2008) Prohibitin: a potential biomarker for tissue based detection of gastric cancer. J Gastroenterol 43:618–625

    Article  PubMed  CAS  Google Scholar 

  • Karakitsos P et al (1998) Evaluation of cytological morphologic criteria and AgNOR expression in male breast lesions. Cytopathology 9:107–113

    PubMed  CAS  Google Scholar 

  • Karhemo PR et al (2011) An extensive tumor array analysis supports tumor suppressive role of nucleophosmin in breast cancer. Am J Pathol 179:1004–1014

    Article  PubMed  CAS  Google Scholar 

  • Karpinska-Kaczmarczyk K et al (2009) Prognostic significance of morphometric parameters of nucleoli and nuclei of invasive ductal breast carcinomas. Pol J Pathol 60:124–129

    PubMed  Google Scholar 

  • Kashiwagi S et al (2011) Advantages of adjuvant chemotherapy for patients with triple negative breast cancer at stage II: usefulness of prognostic markers E-cadherin and Ki67. Breast Cancer Res 13:R122

    Article  PubMed  CAS  Google Scholar 

  • Kessels MM et al (1998) Subcellular localization of estradiol receptor in MCF7 cells studied with nanogold-labelled antibody fragments. Eur J Histochem 42:259–270

    PubMed  CAS  Google Scholar 

  • Kidd M et al (2006) The role of genetic markers – NAP1L1, MAGE-D2, and MTA1 in defining small intestinal carcinoid neoplasia. Ann Surg Oncol 13:253–262

    Article  PubMed  Google Scholar 

  • Kim YJ et al (2008) Suppression of putative tumour suppressor gene GLTSCR2 expression in human glioblastomas. J Pathol 216:218–222

    Article  PubMed  CAS  Google Scholar 

  • Klein and Grummt (1999) Cell cycle-dependent regulation of RNA polymerase I transcription: the nuclolar transcription factor UBF is inactive in mitosis and early G1. Proc Natl Acad Sci U S A 96:6096–6101

    Article  PubMed  CAS  Google Scholar 

  • Kolar Z et al (1992) Argyrophilic nucleolar organizer regions in breast cancer: prognostic significance. Cesk Pathol 28:193–200

    CAS  Google Scholar 

  • Kopper L (2008) Lapatinib: a sword with two edges. Pathol Oncol Res 14:1–8

    Article  PubMed  CAS  Google Scholar 

  • Korsching E et al (2008) Basal carcinoma of the breast revisited: an old entity with new interpretations. J Clin Pathol 61:553–560

    Article  PubMed  CAS  Google Scholar 

  • Koyama H et al (1993) Nucleolar organizer regions in intraductal lesions associated with invasive ductal carcinoma of the breast. Oncology 50:116–120

    Article  PubMed  CAS  Google Scholar 

  • Kumazawa T et al (2011) Novel nucleolar pathway connecting intracellular energy status with p53 activation. J Biol Chem 286:20861–20869

    Article  PubMed  CAS  Google Scholar 

  • Kurt RA et al (2000) Isolation of genes overexpressed in freshly isolated breast cancer specimens. Breast Cancer Res Treat 59:41–48

    Article  PubMed  CAS  Google Scholar 

  • Lacroix and Leclercq (2005) The “portrait” of hereditary breast cancer. Breast Cancer Res Treat 89:297–304

    Article  PubMed  CAS  Google Scholar 

  • Lange CA, Yee D (2011) Killing the second messenger: targeting loss of cell cycle control in endocrine-resistant breast cancer. Endocr Relat Cancer 18:C19–C24

    Article  PubMed  CAS  Google Scholar 

  • Leach SD et al (1998) Enhanced Krev-1 expression inhibits the growth of pancreatic adenocarcinoma cells. Pancreas 16:491–498

    Article  PubMed  CAS  Google Scholar 

  • Lehn S et al (2011) A non-functional retinoblastoma tumor suppressor (RB) pathway in premenopausal breast cancer is associated with resistance to tamoxifen. Cell Cycle 10:956–962

    Article  PubMed  CAS  Google Scholar 

  • Leotoing L et al (2008) Influence of nucleophosmin/B23 on DNA binding and transcriptional activity of the androgen receptor in prostate cancer cell. Oncogene 27:2858–2867

    Article  PubMed  CAS  Google Scholar 

  • Lesty C et al (1992) Nucleoli and AgNOR proteins in 32 cases of primary breast carcinoma. Spatial pattern of interactions between 50 clinical and histometric criteria. Anal Quant Cytol Histol 14:175–186

    PubMed  CAS  Google Scholar 

  • Li M et al (2004) Genes associated with liver metastasis of colon cancer, identified by genome-wide cDNA microarray. Int J Oncol 24:305–312

    PubMed  Google Scholar 

  • Li LY et al (2011) Nuclear ErbB2 enhances translation and cell growth by activating transcription of ribosomal RNA genes. Cancer Res 71:4269–4279

    Article  PubMed  CAS  Google Scholar 

  • Lian Z, Di Cristofano A (2005) Class reunion: PTEN joins the nuclear crew. Oncogene 24:7394–7400

    Article  PubMed  CAS  Google Scholar 

  • Liao DJ, Dickson RB (2000) c-Myc in breast cancer. Endocr Relat Cancer 7:143–164

    Article  PubMed  CAS  Google Scholar 

  • Lin NU et al (2008) Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 26:1993–1999

    Article  PubMed  CAS  Google Scholar 

  • Lin T et al (2010) Tumor initiating function of nucleostemin-enriched mammary tumor cells. Cancer Res 70:9444–9452

    Article  PubMed  CAS  Google Scholar 

  • Lipponen P et al (1993) Nucleolar organizer regions in myofibroblasts in breast cancer. Relation to cancer cell morphometry, flow cytometry, sex steroid receptor content, tumour histology and prognosis. Pathol Res Pract 189:1030–1035

    Article  PubMed  CAS  Google Scholar 

  • Lloreta J et al (2002) Prediction of recurrence and nucleolar features in node-negative breast carcinoma, ductal type, grade II. An ultrastructural study. Virchows Arch 440:280–284

    Article  PubMed  Google Scholar 

  • Lohrum MA et al (2003) Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 3:577–587

    Article  PubMed  CAS  Google Scholar 

  • Lorenzato M et al (2000) Proliferation assessment in breast cancer: a double-staining technique for AgNOR quantification in MIB-1 positive cells especially adapted for image cytometry. Micron 31:151–159

    Article  PubMed  CAS  Google Scholar 

  • Luetkens T et al (2010) Expression, epigenetic regulation and humoral immunogenicity of cancer testis antigen in chronic myeloid leukemia. Leuk Res 34:1647–1655

    Article  PubMed  CAS  Google Scholar 

  • Lynch BJ et al (2001) Elevations of DNA topoisomerase I in invasive carcinoma of the breast. Breast J 7:176–180

    Article  PubMed  CAS  Google Scholar 

  • Ma YL et al (2010) Immunohistochemical analysis revealed CD34 and Ki67 protein expression as significant prognostic factors in colorectal cancer. Med Oncol 27:304–309

    Article  PubMed  CAS  Google Scholar 

  • MacCarty WC (1936) The value of the macronucleolus in the cancer problem. Am J Cancer 26:529–532

    Google Scholar 

  • Maeda K et al (1994) Proliferating cell nuclear antigen labeling index of preoperative biopsy specimens in gastric carcinoma with special reference to prognosis. Cancer 73:528–533

    Article  PubMed  CAS  Google Scholar 

  • Mahata B et al (2011) Recruitment of RPL11 at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and in an Mdm2-dependent manner. Oncogene 31:3060–3071

    Article  PubMed  CAS  Google Scholar 

  • Malakootian M et al (2010) Differential expression of nucleostemin, a stem cell marker, and its variants in different types of brain tumors. Mol Carcinog 49:818–825

    PubMed  CAS  Google Scholar 

  • Malkas LH et al (2006) A cancer associated PCNA expressed in breast cancer has implications as a potential biomarker. Proc Natl Acad Sci U S A 103:19472–19477

    Article  PubMed  CAS  Google Scholar 

  • Marchetti D, Nicolson GL (2001) Human heparanase: a molecular determinant of brain metastasis. Adv Enzyme Regul 41:343–359

    Article  PubMed  CAS  Google Scholar 

  • Marty B et al (2008) Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells. Breast Cancer Res 10:R101

    Article  PubMed  CAS  Google Scholar 

  • Mayer C et al (2004) mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability. Genes Dev 18:423–434

    Article  PubMed  CAS  Google Scholar 

  • McStay B, Grummt I (2008) The epigenetics of rRNA genes: from molecular to chromosome biology. Annu Rev Cell Dev Biol 24:131–157

    Article  PubMed  CAS  Google Scholar 

  • Meaburn KJ, Misteli T (2008) Locus-specific and activity-independent gene repositioning during early tumorigenesis. J Cell Biol 180:39–50

    Article  PubMed  CAS  Google Scholar 

  • Mello ML et al (2008) Image analysis of the AgNOR response in ras-transformed human breast epithelial cells. Acta Histochem 110:210–216

    Article  PubMed  Google Scholar 

  • Merritt MA et al (2009) Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer. BMC Cancer 9:378–390

    Article  PubMed  CAS  Google Scholar 

  • Meyer N, Penn LZ (2008) Reflecting on 25 years with MYC. Nat Rev Cancer 8:976–990

    Article  PubMed  CAS  Google Scholar 

  • Mitra RS et al (2003) Rap1A and rap1B ras-family proteins are prominently expressed in the nucleus of squamous carcinomas: nuclear translocation of GTP-bound active form. Oncogene 22:6243–6256

    Article  PubMed  CAS  Google Scholar 

  • Modlin IM et al (2006) Genetic differentiation of appendiceal tumor malignancy. Ann Surg 244:52–60

    Article  PubMed  Google Scholar 

  • Montanaro L et al (2006) Dyskerin expression influences the level of ribosomal RNA pseudouridylation and telomerase RNA component in human breast cancer. J Pathol 210:10–18

    Article  PubMed  CAS  Google Scholar 

  • Montanaro L et al (2008) Nucleolus, ribosomes, and cancer. Am J Pathol 173:301–310

    Article  PubMed  CAS  Google Scholar 

  • Montanaro L et al (2010) Novel dyskerin-mediated mechanism of p53 inactivation through defective mRNA translation. Cancer Res 70:4767–4777

    Article  PubMed  CAS  Google Scholar 

  • Morris SW et al (1994) Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science 263:1281–1284

    Article  PubMed  CAS  Google Scholar 

  • Moss T (2004) At the crossroads of growth control; making ribosomal RNA. Curr Opin Genet Dev 14:210–217

    Article  PubMed  CAS  Google Scholar 

  • Moss T, Stefanovsky VY (2002) At the center of eukaryotic life. Cell 109:545–548

    Article  PubMed  CAS  Google Scholar 

  • Mourad WA et al (1994) Correlation of two AgNOR counts with Ki-67 labeling index: a study in fine-needle aspirates of lymphoproliferative disorders and breast carcinoma. Diagn Cytopathol 10:113–119

    Article  PubMed  CAS  Google Scholar 

  • Mourmouras V et al (2009) Nucleolin protein expression in cutaneous melanocytic lesions. J Cutan Pathol 36:637–646

    Article  PubMed  Google Scholar 

  • Mueller H et al (2000) Potential prognostic value of mitogen-activated protein kinase activity for disease-free survival of primary breast cancer patients. Int J Cancer 89:384–388

    Article  PubMed  CAS  Google Scholar 

  • Musgrove EA, Sutherland RL (2009) Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 9:631–643

    Article  PubMed  CAS  Google Scholar 

  • Nagashio R et al (2010) Expression of RACK1 is a novel biomarker in pulmonary adenocarcinomas. Lung Cancer 69:54–59

    Article  PubMed  Google Scholar 

  • Nagata Y et al (2004) PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6:117–127

    Article  PubMed  CAS  Google Scholar 

  • Nakayama K, Abe R (1995) Argyrophilic nucleolar organizer region (AgNOR) area per nucleus as a prognostic factor in breast cancer. J Surg Oncol 60:160–167

    Article  PubMed  CAS  Google Scholar 

  • Neumann E et al (1998) Heterogenous expression of the tumor associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell based immunotherapies? Cancer Res 58:4090–4095

    PubMed  CAS  Google Scholar 

  • Ng I et al (1994) Prognostic significance of proliferating cell nuclear antigen expression in hepatocellular carcinoma. Cancer 73:2268–2274

    Article  PubMed  CAS  Google Scholar 

  • Nielsen NH et al (1999) G1-S transition defects occur in most breast cancers and predict outcome. Breast Cancer Res Treat 56:105–112

    Article  PubMed  CAS  Google Scholar 

  • Nielsen DL et al (2009) HER2-targeted therapy in breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Cancer Treat Rev 35:121–136

    Article  PubMed  CAS  Google Scholar 

  • Nozawa Y et al (1996) Expression of nucleophosmin/B23 in normal and neoplastic colorectal mucosa. J Pathol 178:48–52

    Article  PubMed  CAS  Google Scholar 

  • Oberthuer A et al (2004) The tumor associated antigen PRAME is universally expressed in high stage neuroblastoma and associated with poor outcome. Clin Cancer Res 10:4307–4313

    Article  PubMed  CAS  Google Scholar 

  • Ohri AK et al (1992) The relationship between clinical staging, oestrogen receptor status and silver-binding nucleolar organiser regions (AgNOR) in breast carcinoma. Eur J Surg Oncol 18:103–107

    PubMed  CAS  Google Scholar 

  • Oka S et al (2011) The expression of ki-67, but not proliferating cell nuclear antigen, predicts poor disease free survival in patients with adenocarcinoma of the lung. Anticancer Res 31:4277–4282

    PubMed  Google Scholar 

  • Oliveira AM et al (2005) Tumor suppressor genes in breast cancer: the gatekeepers and the caretakers. Am J Clin Pathol 124:S16–S28

    PubMed  CAS  Google Scholar 

  • Onyango P, Feinberg AP (2011) A nucleolar protein, H19 opposite tumor suppressor (HOTS), is a tumor growth inhibitor encoded by a human imprinted H19 antisense transcript. Proc Natl Acad Sci U S A 108:16759–16764

    Article  PubMed  CAS  Google Scholar 

  • O’Regan R, Hawk NN (2011) mTOR inhibition in breast cancer: unraveling the complex mechanisms of mTOR signal transduction and its clinical implications in therapy. Expert Opin Ther Targets 15:859–872

    Article  PubMed  CAS  Google Scholar 

  • Ormandy CJ et al (2003) Cyclin D1, EMS1 and 11q13 amplification in breast cancer. Breast Cancer Res Treat 78:323–335

    Article  PubMed  CAS  Google Scholar 

  • Palacios J et al (2008) The molecular pathology of hereditary breast cancer. Pathobiology 75:85–94

    Article  PubMed  CAS  Google Scholar 

  • Peculis BA (2002) Ribosome biogenesis: ribosomal RNA synthesis as a package deal. Curr Biol 12:R623–R624

    Article  PubMed  CAS  Google Scholar 

  • Pelletier G et al (2000) Competitive recruitment of CBP and Rb-HDAC regulates UBF acetylation and ribosomal transcription. Mol Cell 6:1059–1066

    Article  PubMed  CAS  Google Scholar 

  • Peng L et al (2010) High levels of nucleolar expression of nucleolin are associated with better prognosis in patients with stage II pancreatic ductal adenocarcinoma. Clin Cancer Res 16:3734–3742

    Article  PubMed  CAS  Google Scholar 

  • Perou CM et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  PubMed  CAS  Google Scholar 

  • Pession A et al (1991) The Ag-NOR proteins and transcription and duplication of ribosomal genes in mammalian cell nucleoli. Chromosoma 100:242–250

    Article  PubMed  CAS  Google Scholar 

  • Pezo RC, Singer RH (2008) Nuclear microenvironment in cancer diagnosis and treatment. J Cell Biochem 104:1953–1963

    Article  PubMed  CAS  Google Scholar 

  • Pfau R et al (2008) Members of a family of JmjC domain containing oncoproteins immortalize embryonic fibroblasts via a JmjC domain dependent process. Proc Natl Acad Sci U S A 105:1907–1912

    Article  Google Scholar 

  • Pianese G (1896) Beitrag zur histologie und aetilogie der carcinoma Histologische und experimentelle untersuchungen. Beitr Pathol Anat Allg Pathol 142:1–193

    Google Scholar 

  • Pich A et al (1994) Proliferative activity is a significant prognostic factor in male breast carcinoma. Am J Pathol 145:481–489

    PubMed  CAS  Google Scholar 

  • Pich A et al (2000) Prognostic relevance of AgNORs in tumor pathology. Micron 31:133–141

    Article  PubMed  CAS  Google Scholar 

  • Planchon SM et al (2008) The nuclear affairs of PTEN. J Cell Sci 121(Pt 3):249–253

    Article  PubMed  CAS  Google Scholar 

  • Ploton D et al (1986) Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer region at the optical level. Histochem J 18:5–14

    Article  PubMed  CAS  Google Scholar 

  • Polyak K (2011) Heterogeneity in breast cancer. J Clin Invest 121:3786–3788

    Article  PubMed  CAS  Google Scholar 

  • Poortinga G et al (2004) MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J 23:3325–3335

    Article  PubMed  CAS  Google Scholar 

  • Popescu NC, Zimonjic DB (2002) Chromosome-mediated alterations of the MYC gene in human cancer. J Cell Mol Med 6:151–159

    Article  PubMed  CAS  Google Scholar 

  • Prall OW et al (1998) Estrogen regulation of cell cycle progression in breast cancer cells. J Steroid Biochem Mol Biol 65:169–174

    Article  PubMed  CAS  Google Scholar 

  • Quelle DE et al (1995) Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 83:993–1000

    Article  PubMed  CAS  Google Scholar 

  • Radich JP et al (2006) Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci U S A 103:2794–2799

    Article  PubMed  CAS  Google Scholar 

  • Rajaraman P et al (2010) DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma. Neuro Oncol 12:37–48

    Article  PubMed  CAS  Google Scholar 

  • Rakha E, Reis-Filho JS (2009) Basal-like breast carcinoma: from expression profiling to routine practice. Arch Pathol Lab Med 133:860–868

    PubMed  Google Scholar 

  • Rasinaru A et al (1994) Nucleolar organizer regions (AgNORs) in in situ and invasive components of breast cancers. Rom J Morphol Embryol 40:7–10

    PubMed  CAS  Google Scholar 

  • Ray D et al (2007) Hemizygous disruption of Cdc25A inhibits cellular transformation and mammary tumorigenesis in mice. Cancer Res 67:6605–6611

    Article  PubMed  CAS  Google Scholar 

  • Ray D et al (2011) Cdk2-null mice are resistant to ErbB-2-induced mammary tumorigenesis. Neoplasia 13:439–444

    PubMed  Google Scholar 

  • Raymond WA, Leong AS (1989) Nucleolar organizer regions relate to growth fractions in human breast carcinoma. Hum Pathol 20:741–746

    Article  PubMed  CAS  Google Scholar 

  • Reis-Filho JS, Pusztai L (2011) Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet 378:1812–1823

    Article  PubMed  CAS  Google Scholar 

  • Ren HZ et al (2010) Increased expression of prohibitin and its relationship with poor prognosis in esophageal squamous cell carcinoma. Pathol Oncol Res 16:515–522

    Article  PubMed  CAS  Google Scholar 

  • Robertson JF et al (2009) Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study. J Clin Oncol 27:4530–4535

    Article  PubMed  CAS  Google Scholar 

  • Roller E et al (1993) Nucleolar organizer regions in human breast cancer. Zentralbl Pathol 139:195–199

    PubMed  CAS  Google Scholar 

  • Ross JS et al (2009) The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 14:320–368

    Article  PubMed  CAS  Google Scholar 

  • Roussel P, Hernandez-Verdun D (1994) Identification of Ag-NOR proteins, markers of proliferation related to ribosomal gene activity. Exp Cell Res 214:465–472

    Article  PubMed  CAS  Google Scholar 

  • Roussel P et al (1992) Nucleolin is an Ag-NOR protein; this property is determined by its amino-terminal domain independently of its phosphorylation state. Exp Cell Res 203:259–269

    Article  PubMed  CAS  Google Scholar 

  • Ruggero D, Pandolfi PP (2003) Does the ribosome translate cancer? Nat Rev Cancer 3:179–192

    Article  PubMed  CAS  Google Scholar 

  • Ruggero D et al (2003) Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification. Science 299:259–262

    Article  PubMed  CAS  Google Scholar 

  • Saal LH et al (2005) PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 65:2554–2559

    Article  PubMed  CAS  Google Scholar 

  • Saal LH et al (2007) Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci U S A 104:7564–7569

    Article  PubMed  CAS  Google Scholar 

  • Saal LH et al (2008) Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet 40:102–107

    Article  PubMed  CAS  Google Scholar 

  • Sacks NP et al (1992) Silver-stained nucleolar organiser region counts are of no prognostic value in primary breast cancer. Eur J Surg Oncol 18:98–102

    PubMed  CAS  Google Scholar 

  • Saijo Y et al (2001) Expression of nucleolar protein p120 predicts poor prognosis in patients with stage 1 lung adenocarcinoma. Ann Oncol 12:1121–1125

    Article  PubMed  CAS  Google Scholar 

  • Sanij E, Hannan RD (2009) The role of UBF in regulating the structure and dynamics of transcriptionally active rDNA chromatin. Epigenetics 4:374–382

    Article  PubMed  CAS  Google Scholar 

  • Saporita AJ et al (2011) RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis. Cancer Res 71:6708–6717

    Article  PubMed  CAS  Google Scholar 

  • Sasaki M et al (2010) Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RP11. Nat Med 17:944–952

    Article  CAS  Google Scholar 

  • Sasaki M et al (2011) Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11. Nat Med 17:944–951

    Article  PubMed  CAS  Google Scholar 

  • Sato T et al (1992) The human prohibitin gene located on chromosme 17q21 is mutated in sporadic breast cancer. Cancer Res 52:1643–1646

    PubMed  CAS  Google Scholar 

  • Sato K et al (1999) Expression of p120 nucleolar proliferating antigen in human gliomas and growth suppression of glioma cells by p120 ribozyme vector. Int J Oncol 14:417–424

    PubMed  CAS  Google Scholar 

  • Schmidt EV (1999) The role of c-myc in cellular growth control. Oncogene 18:2988–2996

    Article  PubMed  CAS  Google Scholar 

  • Semba S et al (2010) Requirement of phosphatase of regenerating liver-3 for the nucleolar localization of nucleolin during the progression of colorectal carcinoma. Cancer Sci 101:2254–2261

    Article  PubMed  CAS  Google Scholar 

  • Shao MM et al (2011) A subset of breast cancer predisposes to brain metastasis. Med Mol Morphol 44:15–20

    Article  PubMed  CAS  Google Scholar 

  • Sharma G et al (2007) Promoter hypermethylation of p16INK4A, p14ARF, CyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients. Life Sci 80:1873–1881

    Article  PubMed  CAS  Google Scholar 

  • Sherr CJ (1998) Tumor surveillance via the ARF-p53 pathway. Genes Dev 12:2984–2991

    Article  PubMed  CAS  Google Scholar 

  • Silva J et al (2001) Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer. Oncogene 20:4586–4590

    Article  PubMed  CAS  Google Scholar 

  • Simha M et al (1996) Prognostic value of argyrophylic nucleolar organiser regions (AgNORs) in breast lesions. Indian J Cancer 33:76–85

    PubMed  CAS  Google Scholar 

  • Simin K et al (2004) pRb inactivation in mammary cells reveals common mechanisms for tumor initiation and progression in divergent epithelia. PLoS Biol 2:E22

    Article  PubMed  CAS  Google Scholar 

  • Sinha SK et al (1996) C-erb B2 oncoprotein expression. Correlation with the Ki-67 labeling index and AgNOR counts in breast carcinoma on fine needle aspiration cytology. Acta Cytol 40:1217–1220

    Article  PubMed  CAS  Google Scholar 

  • Sirri V et al (2000) The AgNOR proteins: qualitative and quantitative changes during the cell cycle. Micron 31:121–126

    Article  PubMed  CAS  Google Scholar 

  • Sirri V et al (2008) Nucleolus: the fascinating nuclear body. Histochem Cell Biol 129:13–31

    Article  PubMed  CAS  Google Scholar 

  • Sivridis E, Sims B (1990) Nucleolar organiser regions: new prognostic variable in breast carcinomas. J Clin Pathol 43:390–392

    Article  PubMed  CAS  Google Scholar 

  • Sivridis E et al (1993) The prognostic significance of AgNOR counts in lymph node deposits of breast carcinomas. Pathol Res Pract 189:877–881

    Article  PubMed  CAS  Google Scholar 

  • Slamon DJ et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    Article  PubMed  CAS  Google Scholar 

  • Smith R, Crocker J (1988) Evaluation of nucleolar organizer region-associated proteins in breast malignancy. Histopathology 12:113–125

    Article  PubMed  CAS  Google Scholar 

  • Sorlie T et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874

    Article  PubMed  CAS  Google Scholar 

  • Stefanovsky VY et al (2001) An immediate response of ribosomal transcription to growth factor stimulation in mammals is mediated by ERK phosphorylation of UBF. Mol Cell 8:1063–1073

    Article  PubMed  CAS  Google Scholar 

  • Stefanovsky VY et al (2006) Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. Mol Cell 21:629–639

    Article  PubMed  CAS  Google Scholar 

  • Stendahl M et al (2004) Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients. Br J Cancer 90:1942–1948

    Article  PubMed  CAS  Google Scholar 

  • Stewart TA et al (1984) Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 38:627–637

    Article  PubMed  CAS  Google Scholar 

  • Subramanian S et al (1996) AgNORs and their relationship to cell size, histological grade, lymph node involvement, metastases, and survival pattern in carcinoma of the breast: a study from south India. J Surg Oncol 62:139–143

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto M et al (2003) Nucleolar Arf tumor suppressor inhibits ribosomal RNA processing. Mol Cell 11:415–424

    Article  PubMed  CAS  Google Scholar 

  • Tajrishi MM et al (2011) Nucleolin: the most abundant multifunctional phosphoprotein of nucleolus. Commun Integr Biol 4:267–275

    Article  PubMed  CAS  Google Scholar 

  • Tanaka N et al (2011) Inhibition of PRAME expression causes cell cycle arrest and apoptosis in leukemic cells. Leuk Res 35:1219–1225

    Article  PubMed  CAS  Google Scholar 

  • Thangavel C et al (2011) Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer 18:333–345

    Article  PubMed  CAS  Google Scholar 

  • Tiedemann RE et al (2011) Identification of molecular vulnerabilities in human multiple myeloma cells by RNAi lethality screening of the druggable genome. Cancer Res 72:757–768

    Article  PubMed  CAS  Google Scholar 

  • Toikkanen and Joensuu (1993) AgNOR counts have no prognostic value in breast cancer. J Pathol 169:251–254

    Article  PubMed  CAS  Google Scholar 

  • Tolaney SM, Krop IE (2009) Mechanisms of trastuzumab resistance in breast cancer. Anticancer Agents Med Chem 9:348–355

    Article  PubMed  CAS  Google Scholar 

  • Toma MI et al (2011) Expression of the Forkhead transcription factor FOXP1 is associated with tumor grade and Ki67 expression in clear cell renal cell carcinoma. Cancer Invest 29:123–129

    Article  PubMed  Google Scholar 

  • Trere D et al (1989) The silver-stained proteins of interphasic nucleolar organizer regions as a parameter of cell duplication rate. Exp Cell Res 184:131–137

    Article  PubMed  CAS  Google Scholar 

  • Trere D et al (1991) AgNOR area in interphase nuclei of human tumours correlates with the proliferative activity evaluated by bromodeoxyuridine labelling and Ki-67 immunostaining. J Pathol 165:53–59

    Article  PubMed  CAS  Google Scholar 

  • Trere D et al (2004) Nucleolar size and activity are related to pRb and p53 status in human breast cancer. J Histochem Cytochem 52:1601–1607

    Article  PubMed  CAS  Google Scholar 

  • Tsang CK et al (2010) mTOR binds to the promoters of RNA polymerase I- and III-transcribed genes. Cell Cycle 9:953–957

    Article  PubMed  CAS  Google Scholar 

  • Tsuchiya M et al (2011) Critical role of the nucleolus in activation of the p53-dependent postmitotic checkpoint. Biochem Biophys Res Commun 407:378–382

    Article  PubMed  CAS  Google Scholar 

  • Tsui KH et al (2004) Association of nuclephosmin/B23 mRNA expression with clinical outcome in patients with bladder carcinoma. Urology 64:839–844

    Article  PubMed  Google Scholar 

  • Tsui KH et al (2008) Association of nucleophosmin/B23 with bladder cancer recurrence based on immunohistochemical assessment in clinical samples. Acta Pharmacol Sin 29:364–370

    Article  PubMed  CAS  Google Scholar 

  • Tulchin N et al (1998) Nucleolar localization of BRCA1 protein in human breast cancer. Int J Oncol 13:513–518

    PubMed  CAS  Google Scholar 

  • Tulchin N et al (2010) BRCA1 protein and nucleolin colocalize in breast carcinoma tissue and cancer cell lines. Am J Pathol 176:1203–1214

    Article  PubMed  CAS  Google Scholar 

  • Uchiyama B et al (1997) Expression of nucleolar protein p120 in human lung cancer: difference in histological types of a marker for proliferation. Clin Cancer Res 3:1873–1877

    PubMed  CAS  Google Scholar 

  • Ueki T et al (1997) Significance of the expression of proliferation associated nucleolar antigen p120 in human colorectal tumor. Hum Pathol 28:74–79

    Article  PubMed  CAS  Google Scholar 

  • van Diest PJ et al (1990) Prognostic value of nucleolar morphometric variables in cytological breast cancer specimens. J Clin Pathol 43:157–159

    Article  PubMed  Google Scholar 

  • Varna M et al (2011) TP53 status and response to treatment in breast cancers. J Biomed Biotechnol 2011:284584

    Article  PubMed  CAS  Google Scholar 

  • Vazquez-Martin A et al (2011) Raptor, a positive regulatory subunit of mTOR complex 1, is a novel phosphoprotein of the rDNA transcription machinery in nucleoli and chromosomal nucleolus organizer regions (NORs). Cell Cycle 10:3140–3152

    Article  PubMed  CAS  Google Scholar 

  • Ventura L et al (1999) Nucleolar protein p120 expression in oral carcinoma. Anticancer Res 19:1423–1426

    Google Scholar 

  • Vincent T et al (2008) The glycogen synthase kinase (GSK) 3beta represses RNA polymerase I transcription. Oncogene 27:5254–5259

    Article  PubMed  CAS  Google Scholar 

  • Vogel CL et al (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719–726

    Article  PubMed  CAS  Google Scholar 

  • Voit R et al (1997) Mechanism of repression of RNA polymerase I transcription by the retinoblastoma protein. Mol Cell Biol 17:4230–4237

    PubMed  CAS  Google Scholar 

  • Voit R et al (1999) Phosphorylation by G1-specific cdk-cyclin complexes activates the nucleolar transcription factor UBF. EMBO J 18:1891–1899

    Article  PubMed  CAS  Google Scholar 

  • Voit R and Grummt (2001) Phosphorylation of UBF at serine 388 is required for interaction with RNA polymerase I and activation of rDNA transcription. Proc Natl Acad Sci U S A 98:13631–13636

    Article  PubMed  CAS  Google Scholar 

  • Wang L et al (2009a) Clonal analysis of gastric carcinoma and precancerous lesions and its relation to Ki-67 protein expression. Neoplasma 56:48–55

    Article  PubMed  CAS  Google Scholar 

  • Wang Z et al (2009b) RACK1, an excellent predictor for poor clinical outcome in oral squamous carcinoma, similar to Ki67. Eur J Cancer 45:490–496

    Article  PubMed  CAS  Google Scholar 

  • Weber JD et al (1999) Nucleolar Arf sequesters Mdm2 and activates p53. Nat Cell Biol 1:20–26

    Article  PubMed  CAS  Google Scholar 

  • White RJ (2008) RNA polymerases I and III, non-coding RNAs and cancer. Trends Genet 24:622–629

    Article  PubMed  CAS  Google Scholar 

  • Whyte J et al (2009) Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development. Breast Cancer Res 11:209

    Article  PubMed  CAS  Google Scholar 

  • Williams MD et al (2011) Differential gene expression profiling of aggressive and nonaggressive follicular carcinomas. Hum Pathol 42:1213–1220

    Article  PubMed  CAS  Google Scholar 

  • Witkiewicz AK, Knudsen ES (2011) RB pathway and therapeutic sensitivity: new insights in breast cancer and Tamoxifen therapy. Cell Cycle 10:1525

    Article  PubMed  CAS  Google Scholar 

  • Yang P et al (2005) Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer 103:2363–2372

    Article  PubMed  CAS  Google Scholar 

  • Ye F et al (2008) Stem cell abundent proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells. BMC Cancer 18:108

    Article  CAS  Google Scholar 

  • Yoshida Y et al (1994) A clinicopathological evaluation of nucleolar organizer region proteins in human breast carcinoma. Surg Oncol 3:53–57

    Article  PubMed  CAS  Google Scholar 

  • Yu Q et al (2001) Specific protection against breast cancers by cyclin D1 ablation. Nature 411:1017–1021

    Article  PubMed  CAS  Google Scholar 

  • Yue H, Jiang HY (2005) Expression of cell cycle regulator p57kip2, cyclinE protein and proliferating cell nuclear antigen in human pancreatic cancer: an immunohistochemical study. World J Gastroenterol 11:5057–5060

    PubMed  CAS  Google Scholar 

  • Zaitoun AM, Ebbs SR (2000) Quantitative cytological assessment of Ki67 and AgNORs using computer-digitized image analysis of four clinicopathological breast lesions. Cytopathology 11:243–254

    Article  PubMed  CAS  Google Scholar 

  • Zhai W, Comai L (2000) Repression of RNA polymerase I transcription by the tumor suppressor p53. Mol Cell Biol 20:5930–5938

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Xiong Y (1999) Mutations in human ARF exon 2 disrupt its nucleolar localization and impair its ability to block nuclear export of MDM2 and p53. Mol Cell 3:579–591

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y et al (2003) Ribosomal protein L11 negatively regulates oncoprotein MDM2 and ­mediates a p53-dependent ribosomal-stress checkpoint pathway. Mol Cell Biol 23:8902–8912

    Article  PubMed  CAS  Google Scholar 

  • Zhang C et al (2005) PTEN represses RNA Polymerase I transcription by disrupting the SL1 ­complex. Mol Cell Biol 25:6899–6911

    Article  PubMed  CAS  Google Scholar 

  • Zhang G et al (2010a) Expression of nucleostemin, epidermal growth factor and epidermal growth factor receptor in human esophageal squamous cell carcinoma tissues. J Cancer Res Clin Oncol 136:587–594

    Article  PubMed  CAS  Google Scholar 

  • Zhang L et al (2010b) Epidermal growth factor-induced heparanase nucleolar localization augments DNA topoisomerase I activity in brain metastatic breast cancer. Mol Cancer Res 8:278–290

    Article  PubMed  CAS  Google Scholar 

  • Zhang L et al (2011) MicroRNA-1258 suppresses breast cancer brain metastasis by targeting ­heparanase. Cancer Res 71:645–654

    Article  PubMed  CAS  Google Scholar 

  • Zhao J et al (2003) ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth. Mol Cell 11:405–413

    Article  PubMed  CAS  Google Scholar 

  • Zhong S et al (2004) Epidermal growth factor enhances cellular TATA binding protein levels and induces RNA polymerase I- and III-dependent gene activity. Mol Cell Biol 24:5119–5129

    Article  PubMed  CAS  Google Scholar 

  • Zilli M et al (2009) Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer. Biochim Biophys Acta 1795:62–81

    PubMed  CAS  Google Scholar 

  • Zwart W et al (2011) Estrogen receptor-positive breast cancer: a multidisciplinary challenge. Wiley Interdiscip Rev Syst Biol Med 3:216–230

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada

    Judy Yan & Damu Tang

  2. Division of Urology, Department of Surgery, McMaster University, Hamilton, ON, Canada

    Judy Yan & Damu Tang

  3. Father Sean O’Sullivan Research Institute, T3310, St. Joseph’s Hospital, 50 Charlton Ave East, L8N 4A6, Hamilton, ON, Canada

    Judy Yan & Damu Tang

  4. The Hamilton Center for Kidney Research, T3310, St. Joseph’s Hospital, 50 Charlton Ave East, L8N 4A6, Hamilton, ON, Canada

    Judy Yan & Damu Tang

Authors
  1. Judy Yan
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  2. Damu Tang
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Correspondence to Damu Tang .

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  1. , Biology, University of Toronto at Mississauga, Mississauga Rd. N. 3359, Mississauga, L5L1C6, Ontario, Canada

    Danton H O'Day

  2. , Biology, University of Toronto at Mississauga, Mississauga Rd. 3359, Mississauga, L5L1C6, Ontario, Canada

    Andrew Catalano

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Yan, J., Tang, D. (2013). The Nucleolar Aspect of Breast Cancer. In: O'Day, D., Catalano, A. (eds) Proteins of the Nucleolus. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5818-6_12

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