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Human mammary epithelial cells in culture: differentiation and transformation

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Breast Cancer: Cellular and Molecular Biology

Part of the book series: Cancer Treatment and Research ((CTAR,volume 40))

Abstract

The development of human mammary epithelial cell (HMEC) tissue culture systems has permitted these cells to be examined under controlled experimental conditions. Since recourse to in vivo studies is not possible with humans, the fidelity with which the culture system reflects the in vivo situation is particularly important, if the information obtained in vitro is to have meaning for understanding the normal and perturbed functions of the human breast. We describe here our results in developing a system for long term growth of human mammary epithelial cells in monolayer culture [1–4]. While this system is still far from providing an accurate representation of the many different stages of functional differentiation which may occur in the breast, it is a useful beginning to understand control of normal differentiated states, and to examine the multiple steps in the progression from normal to malignantly transformed cells.

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References

  1. Stampfer M, Hallowes RC, and Hackett AJ: Growth of normal human mammary cells in culture. In Vitro 16: 415–425, 1980.

    Article  PubMed  CAS  Google Scholar 

  2. Stampfer MR: Cholera toxin stimulation of human mammary epithelial cells in culture. In Vitro 18: 531–537, 1982.

    Article  PubMed  CAS  Google Scholar 

  3. Hammond SL, Ham RG, Stampfer MR: Serum-free growth of human mammary epithelial cells. Rapid clonal growth in defined medium and extended serial passage with pituitary extract. Natl Acad Sci USA 81: 5435–5439, 1984.

    Article  CAS  Google Scholar 

  4. Stampfer MR: Isolation and growth of human mammary epithelial cells. J Tissue Cult Methd 9: 107–115, 1985.

    Article  Google Scholar 

  5. Smith HS, Wolman SR, Auer G, Hackett AJ: Cell culture studies: a perspective on malignant progression of human breast cancer. In: Breast Cancer: Origins, Detection, and Treatment Rich MA, Hager JC, Taylor-Papdimitriou J, (eds.) Boston, Martinus Nijhoff Publishing, 1985, pp. 75–89.

    Google Scholar 

  6. Stampfer MR, Hackett AJ, Smith HS, Hancock MC, Leung JP, Edgington TS: Growth of human mammary epithelium in culture and expression of tumor specific properties. Cold Spring Harbor Conferences on Cell Proliferation 9: 819–829, 1982.

    Google Scholar 

  7. Smith S, Pasco D, Thompson BJ, Stampfer M, Nandi, S: Thioesterase II, a new marker enzyme for human cells of breast epithelial origin. J Nat Cancer Inst 73: 323–329, 1984.

    PubMed  CAS  Google Scholar 

  8. Stampfer MR, Vlodavsky I, Smith HS, Ford R, Becker F, Riggs J: Fibronectin production by human mammary cells. J Nat Cancer Inst 67: 253–261, 1981

    PubMed  CAS  Google Scholar 

  9. Wolman SR, Smith HS, Stampfer M, Hackett AJ: Growth of diploid cells from breast cancers. Cancer Genet Cytogenet 16: 49–64, 1985.

    Article  PubMed  CAS  Google Scholar 

  10. Meranze DR, Gruenstein M, Shimkin MD: Effect of age and sex on the development of neoplasms in Wistar rats receiving a single intragastric instillation of 7,12-dimethylbenzy(a) anthracene. Int J Cancer 4: 480–484, 1969.

    Article  PubMed  CAS  Google Scholar 

  11. Levin W, Wood AW, Chang RL, Slaga TJ, Yagi H, Jerina DM, Conney AH: Marked differences in the tumor initiating activity of optically pure(+)- and (-)-trans-7,8,dihydroxy-7,8-dihydrobenzo(a)pyrene on mouse skin. Cancer Res 37: 2721–2725, 1977.

    PubMed  CAS  Google Scholar 

  12. Stowers SJ, Anderson MW: Formation and persistence of benzo(a)pyrene metabolite-DNA adducts. Environ Health Perspect 62: 31–40, 1985.

    Article  PubMed  CAS  Google Scholar 

  13. Autrup H, Harris CC: Metabolism of chemical carcinogens by cultured human tissues. In: Human Carcinogenesis, Harris CC and Autrup H (eds). New York, Academic Press, 1983, pp 169–194.

    Google Scholar 

  14. Stampfer MR, Bartholomew JC, Smith HS, Bartley J: Metabolism of benzo(a)pyrene by human mammary epithelial cells: toxicity and DNA adduct formation. Proc Natl Acad Sci USA 78: 6251–6255, 1981.

    Article  PubMed  CAS  Google Scholar 

  15. Bartley JC, Bartholomew JC, Stampfer MR: Metabolism of benzo(a)pyrene in human mammary epithelial and fibroblast cells: metabolite pattern and DNA adduct formation. J Cell Biochem 18: 135–148, 1982.

    Article  PubMed  CAS  Google Scholar 

  16. Bartley JC, Stampfer MR: Factors influencing benzo(a)pyrene metabolism in human mammary epithelial cells in culture. Carcinogenesis 6: 1017–1022, 1985.

    Article  PubMed  CAS  Google Scholar 

  17. Leadon SA, Hanawalt PC: Monoclonal antibody to DNA containing thymine glycol. Mutat Res 112: 191–200, 1983.

    PubMed  CAS  Google Scholar 

  18. DiPaolo JA: Relative difficulties in transforming human and animal cells in vitro. J Natl Cancer Inst 70: 3–8, 1983.

    PubMed  CAS  Google Scholar 

  19. Harris CC: Human tissues and cells in carcinogenesis research. Cancer Res 47: 1–10, 1987.

    PubMed  CAS  Google Scholar 

  20. Chang SE, Keen J, Lane EB, Taylor-Papdimitriou J: Establishment and characterization of SV40 transformed human breast epithelial cell lines. Cancer Res 42: 2040–2053, 1982.

    PubMed  CAS  Google Scholar 

  21. Rhim JS, Gilbert J, Arnstein P, Price FM, Sanford KK, Aaronson SA: Neoplastic transformation of human epidermal keratinocytes by the combined action of adenol2-SV40 virus and Kirsten murine sarcoma virus. Science 1250–1252, 1985.

    Google Scholar 

  22. Yoakum GH, Lechner JF, Gabrielson EW et al. Transformation of human bronchial epithelial cells transfected by Harvey ras oncogene. Science 227: 1174–1179, 1985.

    Article  PubMed  CAS  Google Scholar 

  23. Walen KH, Arnstein P: Induction of tumorigenesis and chromosomal abnormalities in human amniocytes infected with simian virus 40 and Kirsten sarcoma virus. In Vitro 22: 57–65, 1986.

    CAS  Google Scholar 

  24. Rhim JS, Fujita J, Arnstein P, Aaronson SA: Neoplastic conversion of human keratinocytes by adenovirus 12-SV40 virus and chemical carcinogens. Science 232: 385–388, 1986.

    Article  PubMed  CAS  Google Scholar 

  25. Arklie J, Taylor-Papadimitriou J, Bodmer W, Egan M, Millis R: Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers. Int J Cancer 28: 23–29, 1981.

    Article  PubMed  CAS  Google Scholar 

  26. Masui T, Wakefield LM, Lechner JF, LaVeck MA, Sporn MB, Harris, CC Type β transforming growth factor: a differentiation-inducing serum factor for normal human bronchial epithelial cells. Proc Natl Acad Sci USA 83: 2438–2442, 1986.

    Article  PubMed  CAS  Google Scholar 

  27. Shipley GD, Pittelkow MR, Wille JJ, Scott RE, Moses, HL: Reversible inhibition of normal human prokeratinocyte proliferation by type β transforming growth factor-growth inhibitor in serum-free medium. Cancer Res 46: 2068–2071, 1986.

    PubMed  CAS  Google Scholar 

  28. Stampfer MR, Bartley JC: Induction of transformation and continuous cell lines from normal human mammary epithelial cells after exposure to benzo(a)pyrene. Proc Natl Acad Sci USA 82: 2394–2398, 1985.

    Article  PubMed  CAS  Google Scholar 

  29. Clark R, Stampfer MR, Milley B, O’Rourke E, Walen K, Kreigler M, Kopplin J, McCormick, F: Transformation of human mammary epithelial cells by oncogenic retroviruses. Cancer Research, in press.

    Google Scholar 

  30. Walen KH, Stampfer MR: Karyotypic changes in human mammary epithelial cells transformed in vitro. Submitted to Cancer Genet Cytogenet.

    Google Scholar 

  31. Bates SE, Valverius E, Salomon D, Stampfer M, Lippman ME, Dickson RB: Expression and estrogen regulation of transforming growth factor-α mRNA in human breast cancer. Proc Am Assoc Cancer Res 28: 233, 1987.

    Google Scholar 

  32. Wicha MS, Lowrie G, Kohn E, Bayavandoss P, Mahn T: Extracellular matrix promotes mammary epithelial growth and differentiation in vitro. Proc Natl Acad Sci USA 79: 3213–3217, 1982.

    Article  PubMed  CAS  Google Scholar 

  33. Lee EY-H, Lee WH, Kaetzel CS, Parry G, Bissell MJ: Interaction of mouse mammary epithelial cells with collagen substrata: Regulation of casein gene expression and secretion. Proc Natl Acad Sci USA 82: 1419–1423, 1985.

    Article  PubMed  CAS  Google Scholar 

  34. Emerman JT, Bartley JC, Bissell MJ: Glucose metabolite patterns as markers of functional differentiation in freshly isolated and cultured mouse mammary epithelial cells. Exp Cell Res 134:241–250, 1981.

    Article  PubMed  CAS  Google Scholar 

  35. Parry G, Cullen B, Kaetzel CS, Kramer R, Moss L: Regulation of differentiation and polarized secretion in mammary epithelial cells maintained in culture: Extracellular matrix and membrane polarity influences. Submitted to J Cell Biol 1987.

    Google Scholar 

  36. Arklie J, Taylor-Papadimitriou J, Bodmer W, Egan M, Millis R: Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers. Int J Cancer 28: 23–29, 1981.

    Article  PubMed  CAS  Google Scholar 

  37. Ceriani R, Peterson J, Blank E: Variability in surface antigen expression of human breast epithelial cells cultured from normal breast, normal tissue peripheral to breast carcinomas, and breast carcinomas. Cancer Research 44: 3033–3039, 1984.

    PubMed  CAS  Google Scholar 

  38. Moss L, Greenwalt D, Cullen B, Dinh N, Ranken R, Parry G: Cell-to-cell heterogeneity in the expression of carbohydrate based epitopes of a mucin-type glycoprotein on the surface of human mammary carcinoma cells. Submitted to J Cell Physiol, 1987.

    Google Scholar 

  39. Smith S, Pasco D, Nanci S: Biosynthesis of medium-chain fatty acids by mammary epithelial cells from virgin rats. Biochem J 212: 155–159, 1983.

    PubMed  CAS  Google Scholar 

  40. Sachs Leo: Cell differentiation and bypassing genetic defects in the suppression of malignancy. Cancer Res 47: 1981–1986, 1987.

    Google Scholar 

  41. Kleinman HK, McGarvey ML, Hassel JR, Star VL, Cannon FB, Laurie GW, Martin GR: Basement membrane complexes with biological activity. Biochemistry 25: 312–318, 1986.

    Article  PubMed  CAS  Google Scholar 

  42. Kramer RH, Bensch KG, Davidson PM, Karasek MA: Basal lamina formation by cultured microvascular endothelial cells. J Cell Biol 99: 692–698, 1984.

    Article  PubMed  CAS  Google Scholar 

  43. Janss DH, Hillman EA, Malan-Shibley LB, Ben TL: Methods for the isolation and culture on normal human breast epithelial cells. Methods in Cell Biology, Vol 21B, Prescott DM (ed). New York, Academic Press, 1980, pp 107–134.

    Google Scholar 

  44. Terzaghi M, Nettesheim P, Williams ML: Repopulation of denuded tracheal grafts with normal, preneoplastic, and neoplastic epithelial cell populations. Cancer Res 38: 4546–4553, 1978.

    PubMed  CAS  Google Scholar 

  45. Stampfer MR, Bartley JC: Development of human mammary epithelial cell culture systems and their use for studies of carcinogenesis and differentiation. In: In Vitro Models for Cancer Research, Weber M, Sekely L, (eds). Boca Raton, CRC Press, 1986, Vol. 3, pp 11–30.

    Google Scholar 

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© 1988 Kluwer Academic Publishers, Boston/Dordrecht/London

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Stampfer, M.R., Bartley, J.C. (1988). Human mammary epithelial cells in culture: differentiation and transformation. In: Lippman, M.E., Dickson, R.B. (eds) Breast Cancer: Cellular and Molecular Biology. Cancer Treatment and Research, vol 40. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1733-3_1

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  • DOI: https://doi.org/10.1007/978-1-4613-1733-3_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8975-3

  • Online ISBN: 978-1-4613-1733-3

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