ER Re-expression and Re-sensitization to Endocrine Therapies in ER-negative Breast Cancers

Article

Abstract

Breast cancer is the leading cause of cancer amongst women in the westernized world. The presence or absence of ERα in breast cancers is an important prognostic indicator. About 30–40% of breast cancers lack detectable ERα protein. ERα− breast cancers are resistant to endocrine therapies and have a worse prognosis than ERα+ breast cancers. Since expression of ERα is necessary for response to endocrine therapies, investigational studies are ongoing in order to understand the generation of the ERα− phenotype and develop interventions to restore ERα expression in ERα− breast cancers. DNA methylation and chromatin remodeling are two epigenetic mechanisms that have been linked with the lack of ERα expression and in these cases; demethylation of the ERα promoter or treatment with HDAC inhibitors shows promise in restoring ERα expression in ERα− breast cancers. Two additional potential mechanisms underlying generation of the ERα− phenotype involve E6-AP and Src, both of which have been shown to be elevated in ERα− breast cancer and can drive the proteasomal degradation of ERα. Recently, studies have demonstrated that upregulated growth factor signaling due to hyperactive MAPK activity significantly contributes to generation of the ERα− phenotype and that inhibition of MAPK activity can cause re-expression of the ERα and restore sensitivity to endocrine therapies. Given the challenges in treating ERα− breast cancer, understanding and manipulating the cellular mechanisms that effect expression of ERα are imperative in order to restore sensitivity to endocrine therapies and to design novel therapeutics for the treatment of ERα− breast cancers.

Keywords

Breast cancer Estrogen receptor Endocrine therapy MAPK EGFR HER2 HDAC E6-AP Src 

Abbreviations

ERα

estrogen receptor alpha

ERE

estrogen response element

EGF

epidermal growth factor

EGFR

epidermal growth factor receptor

MAPK

mitogen-activated protein kinase

Her2

hairy-related 2

erbB2

v-erb-b2 erythroblastic leukemia viral oncogene homolog 2

TGF-α

transforming growth factor alpha

E2

estradiol

HDAC

histone deacetylase

DNMT

DNA methyltransferase

SAHA

Suberoylanilide hydroxamic acid

AZA

5-aza-2’-deoxycytide

TSA

Trichostatin A

PAK1

p21 protein (Cdc42/Rac)-activated kinase 1

AKT

serine/threonine protein kinase Akt

PR

progesterone receptor

Src

v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog

E6-AP

ubiquitin protein ligase E3A

HSP

heat shock protein

Pl3K

phosphoinositide 3-kinase

SHC

SH2 Containing Protein

PKC

Protein kinase C

ERK

Extracellular Signal Regulated Kinases

JNK

c-Jun N-terminal Kinase

References

  1. 1.
    Allred DC, Mohsin SK, Fuqua SA. Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer 2001;8:47–61.PubMedCrossRefGoogle Scholar
  2. 2.
    American Cancer Society 11–23–2008 Breast Cancer facts and figures 2007–2008, http://www.cancer.org/downloads/STT/BCFF-Final.pdf
  3. 3.
    American Cancer Society 11–23–2008 Cancer facts and figures 2008, http://www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf
  4. 4.
    Anderson E, Clarke RB, Howell A. Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia 1998;3:23–35.PubMedCrossRefGoogle Scholar
  5. 5.
    Aronica SM, Katzenellenbogen BS. Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-I. Mol Endocrinol 1993;7:743–52.PubMedCrossRefGoogle Scholar
  6. 6.
    Ballare C, Bravo AI, Laucella S, Sorin I, Cerdeiro R, Loza J, Sousa MF, Guman N, Mordoh J. DNA synthesis in estrogen receptor-positive human breast cancer takes place preferentially in estrogen receptor-negative cells. Cancer 1989;64:842–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Baylin S, Bestor TH. Altered methylation patterns in cancer cell genomes: cause or consequence? Cancer Cell 2002;1:299–305.PubMedCrossRefGoogle Scholar
  8. 8.
    Bayliss J, Hilger A, Vishnu P, Diehl K, El-Ashry D. Reversal of the estrogen receptor negative phenotype in breast cancer and restoration of antiestrogen response. Clin Cancer Res 2007;13:7029–36.PubMedCrossRefGoogle Scholar
  9. 9.
    Beato M. Gene regulation by steroid hormones. Cell 1989;56:335–44.PubMedCrossRefGoogle Scholar
  10. 10.
    Berkenstam A, Glaumann H, Martin M, Gustafsson JA, Norstedt G. Hormonal regulation of estrogen receptor messenger ribonucleic acid in T47Dco and MCF-7 breast cancer cells. Mol Endocrinol 1989;3:22–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Berthois Y, Dong XF, Roux-Dossetto M, Martin PM. Expression of estrogen receptor and its messenger ribonucleic acid in the MCF-7 cell line: multiparametric analysis of its processing and regulation by estrogen. Mol Cell Endocrinol 1990;74:11–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Bunone G, Briand PA, Miksicek RJ, Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J 1996;15:2174–83.PubMedGoogle Scholar
  13. 13.
    Cao Y, Karin M. NF-kappaB in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia 2003;8:215–23.PubMedCrossRefGoogle Scholar
  14. 14.
    Cheng G, Weihua Z, Warner M, Gustafsson JA. Estrogen receptors ER alpha and ER beta in proliferation in the rodent mammary gland. Proc Natl Acad Sci U S A 2004;101:3739–46.PubMedCrossRefGoogle Scholar
  15. 15.
    Cheung KL, Willsher PC, Pinder SE, Ellis IO, Elston CW, Nicholson RI, Blamey RW, Robertson JF. Predictors of response to second-line endocrine therapy for breast cancer. Breast Cancer Res Treat 1997;45:219–24.PubMedCrossRefGoogle Scholar
  16. 16.
    Chu I, Arnaout A, Loiseau S, Sun J, Seth A, McMahon C, Chun K, Hennessy B, Mills GB, Nawaz Z, Slingerland JM. Src promotes estrogen-dependent estrogen receptor alpha proteolysis in human breast cancer. J Clin Invest 2007;117:2205–15.PubMedCrossRefGoogle Scholar
  17. 17.
    Clark GM, McGuire WL. Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol 1988;15:20–5.PubMedGoogle Scholar
  18. 18.
    Clarke RB, Howell A, Potten CS, Anderson E. Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res 1997;57:4987–91.PubMedGoogle Scholar
  19. 19.
    Creighton CJ, Hilger AM, Murthy S, Rae JM, Chinnaiyan AM, El-Ashry D. Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors. Cancer Res 2006;66:3903–11.PubMedCrossRefGoogle Scholar
  20. 20.
    Crews CM, Alessandrini A, Erikson RL. Erks: their fifteen minutes has arrived. Cell Growth Differ 1992;3:135–42.PubMedGoogle Scholar
  21. 21.
    Danielian PS, White R, Lees JA, Parker MJ. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors. EMBO J 1992;11:1025–1033.PubMedGoogle Scholar
  22. 22.
    DeSombre ER, Thorpe SM, Rose C, Blough RR, Andersen KW, Rasmussen BB, King WJ. Prognostic usefulness of estrogen receptor immunocytochemical assays for human breast cancer. Cancer Res 1986;46:4256s–64s.PubMedGoogle Scholar
  23. 23.
    Dickson RB, et al. Molecular biology of breast cancer. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer, principles & practice of oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005.Google Scholar
  24. 24.
    Digiovanna MP, Chu P, Davison TL, Howe CL, Carter D, Claus EB, Stern DF. Active signaling by HER-2/neu in a subpopulation of HER-2/neu-overexpressing ductal carcinoma in situ: clinicopathological correlates. Cancer Res 2002;62:6667–73.PubMedGoogle Scholar
  25. 25.
    Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998;351:1451–67.CrossRefGoogle Scholar
  26. 26.
    Eckert RL, Mullick A, Rorke EA, Katzenellenbogen BS. Estrogen receptor synthesis and turnover in MCF-7 breast cancer cells measured by a density shift technique. Endocrinology 1984;114:629–37.PubMedGoogle Scholar
  27. 27.
    El Khissiin A, Cleeren A, Borras M, Leclercq G. Protein synthesis is not implicated in the ligand-dependent activation of the estrogen receptor in MCF-7 cells. J Steroid Biochem Mol Biol 1997;62:269–76.PubMedCrossRefGoogle Scholar
  28. 28.
    El-Ashry D, Miller DL, Kharbanda S, Lippman ME, Kern FG. Constitutive Raf-1 kinase activity in breast cancer cells induces both estrogen-independent growth and apoptosis. Oncogene 1997;15:423–35.PubMedCrossRefGoogle Scholar
  29. 29.
    Fan J, Yin WJ, Lu JS, Wang L, Wu J, Wu FY, Di GH, Shen ZZ, Shao ZM. ER alpha negative breast cancer cells restore response to endocrine therapy by combination treatment with both HDAC inhibitor and DNMT inhibitor. J Cancer Res Clin Oncol 2008;134:883–90.PubMedCrossRefGoogle Scholar
  30. 30.
    Fan M, Nakshatri H, Nephew KP. Inhibiting proteasomal proteolysis sustains estrogen receptor-alpha activation. Mol.Endocrinol 2004;18:2603–15.PubMedCrossRefGoogle Scholar
  31. 31.
    Fanelli MA, Vargas-Roig LM, Gago FE, Tello O, Lucero De AR, Ciocca DR. Estrogen receptors, progesterone receptors, and cell proliferation in human breast cancer. Breast Cancer Res Treat 1996;37:217–28.PubMedCrossRefGoogle Scholar
  32. 32.
    Fantl WJ, Johnson DE, Williams LT. Signalling by receptor tyrosine kinases. Annu Rev Biochem 1993;62:453–81.PubMedGoogle Scholar
  33. 33.
    Ferguson AT, Lapidus RG, Baylin SB, Davidson NE. Demethylation of the estrogen receptor gene in estrogen receptor- negative breast cancer cells can reactivate estrogen receptor gene expression. Cancer Res 1995;55:2279–83.PubMedGoogle Scholar
  34. 34.
    Ferguson AT, Vertino PM, Spitzner JR, Baylin SB, Muller MT, Davidson NE. Role of estrogen receptor gene demethylation and DNA methyltransferase.DNA adduct formation in 5-aza-2'deoxycytidine-induced cytotoxicity in human breast cancer cells. J Biol Chem 1997;272:32260–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Gusterson BA. Identification and interpretation of epidermal growth factor and c-erbB-2 overexpression. Eur J Cancer 1992;28:263–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999;17:1474–81.PubMedGoogle Scholar
  37. 37.
    Higgins KA, Perez JR, Coleman TA, Dorshkind K, McComas WA, Sarmiento UM, Rosen CA, Narayanan R. Antisense inhibition of the p65 subunit of NF-kappa B blocks tumorigenicity and causes tumor regression. Proc Natl Acad Sci USA 1993;90:9901–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Hill CS, Treisman R. Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell 1995;80:199–211.PubMedCrossRefGoogle Scholar
  39. 39.
    Holloway JN, Murthy S, El-Ashry D. A cytoplasmic substrate of mitogen-activated protein kinase is responsible for estrogen receptor-alpha down-regulation in breast cancer cells: the role of nuclear factor-kappaB. Mol Endocrinol 2004;18:1396–410.PubMedCrossRefGoogle Scholar
  40. 40.
    Horwitz KB, Jackson TA, Bain DL, Richer JK, Takimoto GS, Tung L. Nuclear receptor coactivators and corepressors. Mol Endocrinol 1996;10:1167–77.PubMedCrossRefGoogle Scholar
  41. 41.
    Ignar-Trowbridge DM, Nelson KG, Bidwell MC, Curtis SW, Washburn TF, McLachlan JA, Korach KS. Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor. Proc Natl Acad Sci USA 1992;89:4658–62.PubMedCrossRefGoogle Scholar
  42. 42.
    Jacquemier JD, Hassoun J, Torrente M, Martin PM. Distribution of estrogen and progesterone receptors in healthy tissue adjacent to breast lesions at various stages–immunohistochemical study of 107 cases. Breast Cancer Res Treat 1990;15:109–17.PubMedCrossRefGoogle Scholar
  43. 43.
    Johnston SR. Acquired tamoxifen resistance in human breast cancer–potential mechanisms and clinical implications. Anticancer Drugs 1997;8:911–30.PubMedCrossRefGoogle Scholar
  44. 44.
    Johnston SR, Saccani-Jotti G, Smith IE, Salter J, Newby J, Coppen M, Ebbs SR, Dowsett M. Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer. Cancer Res 1995;55:3331–8.PubMedGoogle Scholar
  45. 45.
    Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002;3:415–28.PubMedCrossRefGoogle Scholar
  46. 46.
    Kasid A, Lippman ME, Papageorge AG, Lowy DR, Gelmann EP. Transfection of v-rasH DNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity. Science 1985;228:725–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D, Chambon P. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 1995;270:1491–4.PubMedCrossRefGoogle Scholar
  48. 48.
    Keen JC, Davidson NE. The biology of breast carcinoma. Cancer 2003;97:825–33.PubMedCrossRefGoogle Scholar
  49. 49.
    Keen JC, Yan L, Mack KM, Pettit C, Smith D, Sharma D, Davidson NE. A novel histone deacetylase inhibitor, scriptaid, enhances expression of functional estrogen receptor alpha (ER) in ER negative human breast cancer cells in combination with 5-aza 2′-deoxycytidine. Breast Cancer Res Treat 2003;81:177–86.PubMedCrossRefGoogle Scholar
  50. 50.
    Knight WA, Livingston RB, Gregory EJ, McGuire WL. Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 1977;37:4669–71.PubMedGoogle Scholar
  51. 51.
    Kobayashi S, Iwase H, Itoh Y, Fukuoka H, Yamashita H, Kuzushima T, Iwata H, Masaoka A, Kimura N. Estrogen receptor, c-erbB-2 and nm23/NDP kinase expression in the intraductal and invasive components of human breast cancers. Jpn J Cancer Res 1992;83:859–65.PubMedGoogle Scholar
  52. 52.
    Koerner F, Oyama T, Kurosumi M, Maluf H. Ovarian hormone receptors in human mammary stromal cells. J Steroid Biochem Mol Biol 2001;78:285–90.PubMedCrossRefGoogle Scholar
  53. 53.
    Kurebayashi J, Otsuki T, Kunisue H, Tanaka K, Yamamoto S, Sonoo H. Expression levels of estrogen receptor-alpha, estrogen receptor-beta, coactivators, and corepressors in breast cancer. Clin Cancer Res 2000;6:512–8.PubMedGoogle Scholar
  54. 54.
    Lapidus RG, Ferguson AT, Ottaviano YL, Parl FF, Smith HS, Weitzman SA, Baylin SB, Issa JP, Davidson NE. Methylation of estrogen and progesterone receptor gene 5′ CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res 1996;2:805–10.PubMedGoogle Scholar
  55. 55.
    Liu Y, El-Ashry D, Chen D, Ding IY, Kern FG. MCF-7 breast cancer cells overexpressing transfected c-erbB-2 have an in vitro growth advantage in estrogen-depleted conditions and reduced estrogen-dependence and tamoxifen-sensitivity in vivo. Breast Cancer Res Treat 1995;34:97–117.PubMedCrossRefGoogle Scholar
  56. 56.
    Liu ZG, Hsu H, Goeddel DV, Karin M. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappaB activation prevents cell death. Cell 1996;87:565–76.PubMedCrossRefGoogle Scholar
  57. 57.
    Lonard DM, Nawaz Z, Smith CL, O’Malley BW. The 26S proteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha transactivation. Mol Cell 2000;5:939–48.PubMedCrossRefGoogle Scholar
  58. 58.
    Massarweh S, Osborne CK, Jiang S, Wakeling AE, Rimawi M, Mohsin SK, Hilsenbeck S, Schiff R. Mechanisms of tumor regression and resistance to estrogen deprivation and fulvestrant in a model of estrogen receptor-positive, HER-2/neu-positive breast cancer. Cancer Res 2006;66:8266–73.PubMedCrossRefGoogle Scholar
  59. 59.
    McCarthy SA, Samuels ML, Pritchard CA, Abraham JA, McMahon M. Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes. Genes Dev 1995;9:1953–64.PubMedCrossRefGoogle Scholar
  60. 60.
    McGuire WL, Osborne CK, Clark GM, Knight WA III. Steroid hormone receptors and carcinoma of the breast. Am J Physiol 1982;243:E99–102.PubMedGoogle Scholar
  61. 61.
    McGuire WL, Tandon AK, Allred DC, Chamness GC, Clark GM. How to use prognostic factors in axillary node-negative breast cancer patients. J Natl Cancer Inst 1990;82:1006–15.PubMedCrossRefGoogle Scholar
  62. 62.
    McLeskey SW, Zhang L, El-Ashry D, Trock BJ, Lopez CA, Kharbanda S, Tobias CA, Lorant LA, Hannum RS, Dickson RB, Kern FG. Tamoxifen-resistant fibroblast growth factor-transfected MCF-7 cells are cross-resistant in vivo to the antiestrogen ICI 182,780 and two aromatase inhibitors. Clin Cancer Res 1998;4:697–711.PubMedGoogle Scholar
  63. 63.
    Miller DL, El-Ashry D, Cheville AL, Liu Y, McLeskey SW, Kern FG. Emergence of MCF-7 cells overexpressing a transfected epidermal growth factor receptor (EGFR) under estrogen-depleted conditions: evidence for a role of EGFR in breast cancer growth and progression. Cell Growth Differ 1994;5:1263–74.PubMedGoogle Scholar
  64. 64.
    Mitchell DC, Ing NH. Estradiol stabilizes estrogen receptor messenger ribonucleic acid in sheep endometrium via discrete sequence elements in its 3′-untranslated region. Mol Endocrinol 2003;17:562–74.PubMedCrossRefGoogle Scholar
  65. 65.
    Munzone E, Curigliano G, Rocca A, Bonizzi G, Renne G, Goldhirsch A, Nole F. Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy. Breast Cancer Res 2006;8:R4.PubMedCrossRefGoogle Scholar
  66. 66.
    Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet RJ Jr, Sledge GW Jr. Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol 1997;17:3629–39.PubMedGoogle Scholar
  67. 67.
    Nawaz Z, Lonard DM, Dennis AP, Smith CL, O’Malley BW. Proteasome-dependent degradation of the human estrogen receptor. Proc Natl Acad Sci USA 1999;96:1858–62.PubMedCrossRefGoogle Scholar
  68. 68.
    Newby JC, Johnston SR, Smith IE, Dowsett M. Expression of epidermal growth factor receptor and c-erbB2 during the development of tamoxifen resistance in human breast cancer. Clin Cancer Res 1997;3:1643–51.PubMedGoogle Scholar
  69. 69.
    Norris JL, Baldwin AS Jr. Oncogenic Ras enhances NF-kappaB transcriptional activity through Raf-dependent and Raf-independent mitogen-activated protein kinase signaling pathways. J Biol Chem 1999;274:13841–46.PubMedCrossRefGoogle Scholar
  70. 70.
    Oh AS, Lorant LA, Holloway JN, Miller DL, Kern FG, El-Ashry D. Hyperactivation of MAPK induces loss of ERalpha expression in breast cancer cells. Mol Endocrinol 2001;15:1344–59.PubMedCrossRefGoogle Scholar
  71. 71.
    Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000;19:3159–67.PubMedCrossRefGoogle Scholar
  72. 72.
    Osaki A, Toi M, Yamada H, Kawami H, Kuroi K, Toge T. Prognostic significance of expression of c-ERBB-2 oncoprotein in breast cancer patients. Gan To Kagaku Ryoho 1991;18:1181–5.PubMedGoogle Scholar
  73. 73.
    Ottaviano YL, Issa JP, Parl FF, Smith HS, Baylin SB, Davidson NE. Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells. Cancer Res 1994;54:2552–5.PubMedGoogle Scholar
  74. 74.
    Panahy C, Puddefoot JR, Anderson E, Vinson GP, Berry CL, Turner MJ, Brown CL, Goode AW. Oestrogen and progesterone receptor distribution in the cancerous breast. Br J Cancer 1987;55:459–62.PubMedGoogle Scholar
  75. 75.
    Pearson G, English JM, White MA, Cobb MH. ERK5 and ERK2 cooperate to regulate NF-kappaB and cell transformation. J Biol Chem 2001;276:7927–31.PubMedCrossRefGoogle Scholar
  76. 76.
    Perren TJ. c-erbB-2 oncogene as a prognostic marker in breast cancer. Br J Cancer 1991;63:328–32.PubMedGoogle Scholar
  77. 77.
    Petersen OW, Hoyer PE, van DB. Frequency and distribution of estrogen receptor-positive cells in normal, nonlactating human breast tissue. Cancer Res 1987;47:5748–51.PubMedGoogle Scholar
  78. 78.
    Pietras RJ, Arboleda J, Reese DM, Wongvipat N, Pegram MD, Ramos L, Gorman CM, Parker MG, Sliwkowski MX, Slamon DJ. HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene 1995;10:2435–46.PubMedGoogle Scholar
  79. 79.
    Ramamoorthy S, Nawaz Z. E6-associated protein (E6-AP) is a dual function coactivator of steroid hormone receptors. Nucl Recept Signal 2008;6:e006.PubMedGoogle Scholar
  80. 80.
    Read LD, Greene GL, Katzenellenbogen BS. Regulation of estrogen receptor messenger ribonucleic acid and protein levels in human breast cancer cell lines by sex steroid hormones, their antagonists, and growth factors. Mol Endocrinol 1989;3:295–304.PubMedCrossRefGoogle Scholar
  81. 81.
    Ree AH, Landmark BF, Eskild W, Levy FO, Lahooti H, Jahnsen T, Aakvaag A, Hansson V. Autologous down-regulation of messenger ribonucleic acid and protein levels for estrogen receptors in MCF-7 cells: an inverse correlation to progesterone receptor levels. Endocrinology 1989;124:2577–83.PubMedCrossRefGoogle Scholar
  82. 82.
    Roger P, Daures JP, Maudelonde T, Pignodel C, Gleizes M, Chapelle J, Marty-Double C, Baldet P, Mares P, Laffargue F, Rochefort H. Dissociated overexpression of cathepsin D and estrogen receptor alpha in preinvasive mammary tumors. Hum Pathol 2000;31:593–600.PubMedCrossRefGoogle Scholar
  83. 83.
    Saceda M, Lindsey RK, Solomon H, Angeloni SV, Martin MB. Estradiol regulates estrogen receptor mRNA stability. J Steroid Biochem Mol Biol 1998;66:113–20.PubMedCrossRefGoogle Scholar
  84. 84.
    Saceda M, Lippman ME, Chambon P, Lindsey RL, Ponglikitmongkol M, Puente M, Martin MB. Regulation of the estrogen receptor in MCF-7 cells by estradiol. Mol Endocrinol 1988;2:1157–62.PubMedCrossRefGoogle Scholar
  85. 85.
    Sainsbury JR, Farndon JR, Harris AL, Sherbet GV. Epidermal growth factor receptors on human breast cancers. Br J Surg 1985;72:186–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Sainsbury JR, Farndon JR, Needham GK, Malcolm AJ, Harris AL. Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1987;1:1398–402.PubMedGoogle Scholar
  87. 87.
    Sharma AK, Horgan K, Douglas-Jones A, McClelland R, Gee J, Nicholson R. Dual immunocytochemical analysis of oestrogen and epidermal growth factor receptors in human breast cancer. Br J Cancer 1994a;69:1032–7.PubMedGoogle Scholar
  88. 88.
    Sharma AK, Horgan K, McClelland RA, Douglas-Jones AG, van AT, Dorssers LC, Nicholson RI. A dual immunocytochemical assay for oestrogen and epidermal growth factor receptors in tumour cell lines. Histochem J 1994b;26:306–10.PubMedCrossRefGoogle Scholar
  89. 89.
    Shibata H, Spencer TE, Onate SA, Jenster G, Tsai SY, Tsai MJ, O’Malley BW. Role of co-activators and co-repressors in the mechanism of steroid/thyroid receptor action. Recent Prog Horm Res 1997;52:141–64.PubMedGoogle Scholar
  90. 90.
    Shoker BS, Jarvis C, Clarke RB, Anderson E, Hewlett J, Davies MP, Sibson DR, Sloane JP. Estrogen receptor-positive proliferating cells in the normal and precancerous breast. Am J Pathol 1999a;155:1811–5.PubMedGoogle Scholar
  91. 91.
    Shoker BS, Jarvis C, Sibson DR, Walker C, Sloane JP. Oestrogen receptor expression in the normal and pre-cancerous breast. J Pathol 1999b;188:237–44.PubMedCrossRefGoogle Scholar
  92. 92.
    Siebenlist U, Franzoso G, Brown K. Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol 1994;10:405–55.PubMedCrossRefGoogle Scholar
  93. 93.
    Silverstrini R, Daidone MG, Di FG. Relationship between proliferative activity and estrogen receptors in breast cancer. Cancer 1979;44:665–70.PubMedCrossRefGoogle Scholar
  94. 94.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987;235:177–82.PubMedCrossRefGoogle Scholar
  95. 95.
    Tang CK, Perez C, Grunt T, Waibel C, Cho C, Lupu R. Involvement of heregulin-beta2 in the acquisition of the hormone-independent phenotype of breast cancer cells. Cancer Res 1996;56:3350–8.PubMedGoogle Scholar
  96. 96.
    Terenius L, Johansson H, Rimsten A, Thoren L. Malignant and benign human mammary disease: estrogen binding in relation to clinical data. Cancer 1974;33:1364–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Thomas G. MAP kinase by any other name smells just as sweet. Cell 1992;68:3–6.PubMedCrossRefGoogle Scholar
  98. 98.
    Toi M, Nakamura T, Mukaida H, Wada T, Osaki A, Yamada H, Toge T, Niimoto M, Hattori T. Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer. Cancer 1990;65:1980–4.PubMedCrossRefGoogle Scholar
  99. 99.
    Tora L, White J, Brou C, Tasset D, Webster N, Scheer E, Chambon P. The human estrogen receptor has two independent nonacidic transcriptional activation functions. Cell 1989;59:477–87.PubMedCrossRefGoogle Scholar
  100. 100.
    Torchia J, Glass C, Rosenfeld MG. Co-activators and co-repressors in the integration of transcriptional responses. Curr Opin Cell Biol 1998;10:373–83.PubMedCrossRefGoogle Scholar
  101. 101.
    Troppmair J, Hartkamp J, Rapp UR. Activation of NF-kappa B by oncogenic Raf in HEK 293 cells occurs through autocrine recruitment of the stress kinase cascade. Oncogene 1998;17:685–90.PubMedCrossRefGoogle Scholar
  102. 102.
    Truss M, Beato M. Steroid hormone receptors: interaction with deoxyribonucleic acid and transcription factors. Endocr Rev 1993;14:459–79.PubMedGoogle Scholar
  103. 103.
    Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990;61:203–12.PubMedCrossRefGoogle Scholar
  104. 104.
    van Agthoven T, Timmermans M, Foekens JA, Dorssers LC, Henzen-Logmans SC. Differential expression of estrogen, progesterone, and epidermal growth factor receptors in normal, benign, and malignant human breast tissues using dual staining immunohistochemistry. Am J Pathol 1994;144:1238–46.PubMedGoogle Scholar
  105. 105.
    Wittliff JL, Hilf R, Brooks WF Jr, Savlov ED, Hall TC, Orlando RA. Specific estrogen-binding capacity of the cytoplasmic receptor in normal and neoplastic breast tissues of humans. Cancer Res 1972;32:1983–92.PubMedGoogle Scholar
  106. 106.
    Yamamoto KR. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet 1985;19:209–52.PubMedCrossRefGoogle Scholar
  107. 107.
    Yan L, Nass SJ, Smith D, Nelson WG, Herman JG, Davidson NE. Specific inhibition of DNMT1 by antisense oligonucleotides induces re-expression of estrogen receptor-alpha (ER) in ER-negative human breast cancer cell lines. Cancer Biol Ther 2003;2:552–6.PubMedGoogle Scholar
  108. 108.
    Yang X, Ferguson AT, Nass SJ, Phillips DL, Butash KA, Wang SM, Herman JG, Davidson NE. Transcriptional activation of estrogen receptor alpha in human breast cancer cells by histone deacetylase inhibition. Cancer Res 2000;60:6890–4.PubMedGoogle Scholar
  109. 109.
    Yang X, Phillips DL, Ferguson AT, Nelson WG, Herman JG, Davidson NE. Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells. Cancer Res 2001;61:7025–9.PubMedGoogle Scholar
  110. 110.
    Zhou Q, Atadja P, Davidson NE. Histone deacetylase inhibitor LBH589 reactivates silenced estrogen receptor alpha (ER) gene expression without loss of DNA hypermethylation. Cancer Biol Ther 2007;6:64–9.PubMedGoogle Scholar
  111. 111.
    Zhou Q, Shaw PG, Davidson NE. Inhibition of histone deacetylase suppresses EGF signaling pathways by destabilizing EGFR mRNA in ER-negative human breast cancer cells. Breast Cancer Res Treat 2008, in pressGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.University of Miami, Miller School of MedicineDepartment of Medicine, Sylvester Comprehensive Cancer CenterMiamiUSA

Personalised recommendations