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Breast Cancer Subtypes: Two Decades of Journey from Cell Culture to Patients

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Human Cell Transformation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 720))

Abstract

Recent molecular profiling has identified six major subtypes of breast cancers that exhibit different survival outcomes for patients. To address the origin of different subtypes of breast cancers, we have now identified, isolated, and immortalized (using hTERT) mammary stem/progenitor cells which maintain their stem/progenitor properties even after immortalization. Our decade long research has shown that these stem/progenitor cells are highly susceptible to oncogenesis. Given the emerging evidence that stem/progenitor cells are precursors of cancers and that distinct subtypes of breast cancer have different survival outcome, these cellular models provide novel tools to understand the oncogenic process leading to various subtypes of breast cancers and for future development of novel therapeutic strategies to treat different subtypes of breast cancers.

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References

  1. American Cancer Society. Cancer facts and figures 2011

    Google Scholar 

  2. Morrow PK, Hortobagyi GN (2009) Management of breast cancer in the genome era. Annu Rev Med 60:153–165

    Article  PubMed  CAS  Google Scholar 

  3. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423

    Article  PubMed  CAS  Google Scholar 

  4. Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, Perou CM (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7:96

    Article  PubMed  Google Scholar 

  5. Wazer DE, Liu XL, Chu Q, Gao Q, Band V (1995) Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 E6 or E7. Proc Natl Acad Sci U S A 92(9):3687–3691

    Article  PubMed  CAS  Google Scholar 

  6. Dimri G, Band H, Band V (2005) Mammary epithelial cell transformation: insights from cell culture and mouse models. Breast Cancer Res 7(4):171–179, Review

    Article  PubMed  CAS  Google Scholar 

  7. Cardiff RD, Wellings SR (1999) The comparative pathology of human and mouse mammary glands. J Mammary Gland Biol Neoplasia 4:105–122

    Article  PubMed  CAS  Google Scholar 

  8. Kordon EC, Smith GH (1998) An entire functional mammary gland may comprise the progeny from a single cell. Development 125:1921–1930

    PubMed  CAS  Google Scholar 

  9. Marx J (2003) Cancer research. Mutant stem cells may seed cancer. Science 301:1308–1310

    Article  PubMed  CAS  Google Scholar 

  10. Smith GH, Chepko G (2001) Mammary epithelial stem cells. Microsc Res Tech 52:190–203

    Article  PubMed  CAS  Google Scholar 

  11. Stingl J, Eaves CJ, Zandieh I, Emerman JT (2001) Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue. Breast Cancer Res Treat 67:93–109

    Article  PubMed  CAS  Google Scholar 

  12. Stingl J, Eaves CJ, Kuusk U, Emerman JT (1998) Phenotypic and functional characterization in vitro of a multipotent epithelial cell present in the normal adult human breast. Differentiation 63:201–213

    Article  PubMed  CAS  Google Scholar 

  13. Gudjonsson T, Villadsen R, Nielsen HL, Ronnov-Jessen L, Bissell MJ, Petersen OW (2002) Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties. Genes Dev 16:693–706

    Article  PubMed  CAS  Google Scholar 

  14. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270

    Article  PubMed  CAS  Google Scholar 

  15. Dick JE (2003) Breast cancer stem cells revealed. Proc Natl Acad Sci U S A 100:3547–3549

    Article  PubMed  CAS  Google Scholar 

  16. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983–3988

    Article  PubMed  CAS  Google Scholar 

  17. Band V, Sager R (1989) Distinctive traits of normal and tumor-derived human mammary epithelial cells expressed in a medium that supports long-term growth of both cell types. Proc Natl Acad Sci U S A 86(4):1249–1253

    Article  PubMed  CAS  Google Scholar 

  18. Band V (2003) In vitro models of early neoplastic transformation of human mammary epithelial cells. Methods Mol Biol 223:237–248

    PubMed  CAS  Google Scholar 

  19. Ratsch SB, Gao Q, Srinivasan S, Wazer DE, Band V (2001) Multiple genetic changes are required for efficient immortalization of different subtypes of normal human mammary epithelial cells. Radiat Res 155 (1 Pt 2):143–150, Review

    Article  PubMed  CAS  Google Scholar 

  20. Zhao X, Malhotra GK, Lele SM, Lele MS, West WW, Eudy JD, Band H, Band V (2010) Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate. Proc Natl Acad Sci U S A 107(32):14146–14151

    Article  PubMed  CAS  Google Scholar 

  21. Sleeman KE, Kendrick H, Robertson D, Isacke CM, Ashworth A, Smalley MJ (2007) Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. J Cell Biol 176(1):19–26

    Article  PubMed  CAS  Google Scholar 

  22. Chiba S (2006) Notch signaling in stem cell systems. Stem Cells 24(11):2437–2447

    Article  PubMed  CAS  Google Scholar 

  23. Ruiz i Altaba A, Sanchez P, Dahmane N (2002) Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer 2(5):361–372

    Article  PubMed  CAS  Google Scholar 

  24. Nusse R (2008) Wnt signaling and stem cell control. Cell Res 18(5):523–527, Review

    Article  PubMed  CAS  Google Scholar 

  25. Chambers I, Smith A (2004) Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23(43):7150–7160

    Article  PubMed  CAS  Google Scholar 

  26. Gao Q, Hauser SH, Liu XL, Wazer DE, Madoc-Jones H, Band V (1996) Mutant p53-induced immortalization of primary human mammary epithelial cells. Cancer Res 56(13):3129–3133

    PubMed  CAS  Google Scholar 

  27. Zhao X, Lu L, Pokhriyal N, Ma H, Duan L, Lin S, Jafari N, Band H, Band V (2009) Overexpression of RhoA induces preneoplastic transformation of primary mammary epithelial cells. Cancer Res 69(2):483–491

    Article  PubMed  CAS  Google Scholar 

  28. Dimri GP, Martinez JL, Jacobs JJ, Keblusek P, Itahana K, Van Lohuizen M, Campisi J, Wazer DE, Band V (2002) The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Res 62(16):4736–4745

    PubMed  CAS  Google Scholar 

  29. Nonet GH, Stampfer MR, Chin K, Gray JW, Collins CC, Yaswen P (2001) The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells. Cancer Res 61(4):1250–1254

    PubMed  CAS  Google Scholar 

  30. Band V (1995) Preneoplastic transformation of human mammary epithelial cells. Semin Cancer Biol 6(3):185–192, Review

    Article  PubMed  CAS  Google Scholar 

  31. Band V (1998) The role of retinoblastoma and p53 tumor suppressor pathways in human mammary epithelial cell immortalization. Int J Oncol 12(3): ­499–507, Review

    PubMed  CAS  Google Scholar 

  32. Huibregtse JM, Scheffner M, Howley PM (1991) A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J 10(13):4129–4135

    PubMed  CAS  Google Scholar 

  33. Münger K, Scheffner M, Huibregtse JM, Howley PM (1992) Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. Cancer Surv 12:197–217, Review

    PubMed  Google Scholar 

  34. Gao Q, Srinivasan S, Boyer SN, Wazer DE, Band V (1999) The E6 oncoproteins of high-risk papillomaviruses bind to a novel putative GAP protein, E6TP1, and target it for degradation. Mol Cell Biol 19(1):733–744

    PubMed  CAS  Google Scholar 

  35. Kumar A, Zhao Y, Meng G, Zeng M, Srinivasan S, Delmolino LM, Gao Q, Dimri G, Weber GF, Wazer DE, Band H, Band V (2002) Human papillomavirus oncoprotein E6 inactivates the transcriptional coactivator human ADA3. Mol Cell Biol 22:5801–5812

    Article  PubMed  CAS  Google Scholar 

  36. Zeng M, Kumar A, Meng G, Gao Q, Dimri G, Wazer D, Band H, Band V (2002) Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator. J Biol Chem 277:45611–45618

    Article  PubMed  CAS  Google Scholar 

  37. Meng G, Zhao Y, Nag A, Zeng M, Dimri G, Gao Q, Wazer DE, Kumar R, Band H, Band V (2004) Human ADA3 binds to estrogen receptor (ER) and functions as a coactivator for ER-mediated transactivation. J Biol Chem 279:54230–54240

    Article  PubMed  CAS  Google Scholar 

  38. Gao Q, Kumar A, Srinivasan S, Singh L, Mukai H, Ono Y, Wazer DE, Band V (2000) PKN binds and phosphorylates human papillomavirus E6 oncoprotein. J Biol Chem 275(20):14824–14830

    Article  PubMed  CAS  Google Scholar 

  39. Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD (2000) MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet 26:484–489

    Article  PubMed  CAS  Google Scholar 

  40. Zhao Y, Katzman RB, Delmolino LM, Bhat I, Zhang Y, Gurumurthy CB, Germaniuk-Kurowska A, Reddi HV, Solomon A, Zeng MS, Kung A, Ma H, Gao Q, Dimri G, Stanculescu A, Miele L, Wu L, Griffin JD, Wazer DE, Band H, Band V (2007) The notch regulator MAML1 interacts with p53 and functions as a coactivator. J Biol Chem 282(16):11969–11981, Epub 2007 Feb 22

    Article  PubMed  CAS  Google Scholar 

  41. Zhang Y, Chen J, Gurumurthy CB, Kim J, Bhat I, Gao Q, Dimri G, Lee SW, Band H, Band V (2006) The human orthologue of Drosophila ecdysoneless protein interacts with p53 and regulates its function. Cancer Res 66(14):7167–7175

    Article  PubMed  CAS  Google Scholar 

  42. Kim JH, Gurumurthy CB, Naramura M, Zhang Y, Dudley AT, Doglio L, Band H, Band V (2009) Role of mammalian Ecdysoneless in cell cycle regulation. J Biol Chem 284(39):26402–26410

    Article  PubMed  CAS  Google Scholar 

  43. Kim JH, Gurumurthy CB, Band H, Band V (2010) Biochemical characterization of human Ecdysoneless reveals a role in transcriptional regulation. Biol Chem 391(1):9–19

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank the past and present members of their laboratories that have contributed to work published from our laboratories. Work in our laboratories was supported by the NIH Grants R01CA096844 and R01CA 144027 (VB), and R01CA099163, R01CA116552, R01CA105489, and R01CA087986 (HB) and department of defense breast cancer program W81XWH-07-1-0351 and W81XWH-11-1-0171 (VB), and W81XWH-11-1-0166 (HB) and Eppley Cancer Center Grant.

Author information

Authors and Affiliations

  1. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USA

    Xiangshan Zhao & Vimla Band

  2. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA

    Channabasavaiah Basavaraju Gurumurthy, Gautam Malhotra, Sameer Mirza, Shakur Mohibi, Aditya Bele, Meghan G. Quinn & Hamid Band

  3. Eppley Institute for Cancer and Allied Diseases and UNMC-Eppley Cancer Center, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USA

    Hamid Band & Vimla Band

Authors
  1. Xiangshan Zhao
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  2. Channabasavaiah Basavaraju Gurumurthy
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  3. Gautam Malhotra
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  4. Sameer Mirza
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  5. Shakur Mohibi
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  6. Aditya Bele
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  7. Meghan G. Quinn
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  8. Hamid Band
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  9. Vimla Band
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Corresponding author

Correspondence to Vimla Band .

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Editors and Affiliations

  1. Uniformed Services, Department of Surgery, University of the Health Sciences, South Glen Road 11455, Bethesda, 20854, Maryland, USA

    Johng S. Rhim

  2. , Department of Medicine, McGill University Health Centre, Pine Ave 687, Montreal, Québec, Canada

    Richard Kremer

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Zhao, X. et al. (2011). Breast Cancer Subtypes: Two Decades of Journey from Cell Culture to Patients. In: Rhim, J., Kremer, R. (eds) Human Cell Transformation. Advances in Experimental Medicine and Biology, vol 720. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0254-1_11

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