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Human breast cancer cell lines as models of growth regulation and disease progression

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Abstract

The routine isolation and culture of human breast cancer cells from patients samples has been a goal of breast cancer cell biologists for over 30 years. Despite extensive work in this area and the development of many human breast cancer cell lines, the proportion of patient samples that give rise to immortalized breast cancer cell lines is still disappointingly low. The majority of human breast cancer cell lines that have been established were isolated many years ago and have been grown continuously under poorly defined culture conditions. These cell lines have been useful for studies of the estrogen receptor biology in human breast cancer cells, in identifying growth factors synthesized by breast cancer cells, and for the characterization of genetic alterations in oncogenes and tumor suppressor genes present in these cells. More recently, tissue culture methods have improved, resulting in the ability to culture routinely normal human mammary epithelial cells of specific lineages and this has resulted in the development of new human breast cancer cell lines. The ability to isolate and culture normal and neoplastic human mammary epithelial cells under similar culture conditions has improved these models dramatically and has resulted in the identification of altered cellular phenotypes of human breast cancer cells.

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References

  1. H. D. Soule, J. Vazques, A. Long, S. Albert, and M. Brennan (1973). A human cell line from a pleural effusion derived from a breast carcinoma.J. Natl. Cancer Inst. 511409–1416.

    PubMed  Google Scholar 

  2. E. Y. Lasfargues and L. Ozzello (1958). Cultivation of human breast carcinomas.J. Natl. Cancer Inst. 211131–1147.

    PubMed  Google Scholar 

  3. Y. V. Dobrynn (1963). Establishment and characteristics of cell strains from some epithelial tumors of human origin.J. Natl. Cancer Inst. 311173–1196.

    PubMed  Google Scholar 

  4. G. Trempe and J. Fogh (1973). Variation in characteristics of human tumor cell lines derived from similar tumors.In Vitro 8433.

    Google Scholar 

  5. R. Cailleau, R. Young, M. Olive, and W. J. J. Reeves (1974). Breast tumor cell lines from pleural effusions.J. Natl. Cancer Inst. 53661–666.

    PubMed  Google Scholar 

  6. S. C. Brooks, E. R. Locke, and H. D. Soule (1973). Estrogen receptor in a human cell line (MCF-7) from breast carcinoma.J. Biol. Chem. 2486251–6253.

    PubMed  Google Scholar 

  7. H. D. Soule and C. M. McGrath (1980). Estrogen responsive proliferation of clonal human breast carcinoma cells in athymic mice.Cancer Lett. 10177–189.

    Article  PubMed  Google Scholar 

  8. D. Barnes and G. Sato (1979). Growth of a human mammary tumour cell line in a serum-free medium.Nature 281388–389.

    PubMed  Google Scholar 

  9. Y. Berthois, J. A. Katzenellenbogen, and B. S. Katzenellenbogen (1986). Phenol red in tissue culture media is a weak estrogen: Implications concerning the study of estrogen-responsive cells in culture.Proc. Natl. Acad. Sci. USA 832496–2500.

    PubMed  Google Scholar 

  10. S. E. Pratt and M. N. Pollak (1993). Estrogen and antiestrogen modulation of MCF-7 human breast cancer cell proliferation is associated with specific alterations in accumulation of insulin-like growth factor-binding proteins in conditioned media.Cancer Res. 535193–5198.

    PubMed  Google Scholar 

  11. A. Aakvaag, E. Utaaker, T. Thorsen, O. A. Lea, and H. Lahooti (1990). Growth control of human mammary cancer cells (MCF-7 cells) in culture: Effect of estradiol and growth factors in serum-containing medium.Cancer Res. 507806–7810.

    PubMed  Google Scholar 

  12. K. P. Karey and D. A. Sirbasku (1988). Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17B-estradiol.Cancer Res. 484083–4092.

    PubMed  Google Scholar 

  13. R. B. Dickson, S. E. Bates, M. E. McMananway, and M. E. Lippman (1986). Characterization of estrogen responsive transforming activity in human breast cancer cell lines.Cancer Res. 461707–1713.

    PubMed  Google Scholar 

  14. R. B. Dickson, K. K. Huff, E. M. Spencer, and M. E. Lippman (1985). Induction of epidermal growth factor related polypeptides by 17β-estradiol in MCF-7 human breast cancer cells.Endocrinology 118138–142.

    Google Scholar 

  15. K. K. Huff, C. Knabbe, R. Lindsey, D. Kaufman, D. Bronzert, M. E. Lippman, and R. B. Dickson (1988). Multihormonal regulation of insulin-like growth factor I-related protein in MCF-7 human breast cancer cells.Mol. Endocrinol. 2200–208.

    PubMed  Google Scholar 

  16. K. K. Huff, D. Kaufman, G. H. Gabbay, E. M. Spencer, M. E. Lippman, and R. B. Dickson (1986). Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells.Cancer Res. 464613–4619.

    PubMed  Google Scholar 

  17. M. E. Lippman, R. B. Dickson, A. Kasid, E. Gelmann, N. Davidson, M. McManaway, K. Huff, D. Bronzert, S. Bates, S. Swain, and C. Knabbe (1986). Autocrine and paracrine growth regulation of human breast cancer.J. Steroid Biochem.24147–154.

    Article  PubMed  Google Scholar 

  18. M. E. Lippman, R. B. Dickson, E. P. Gelmann, N. Rosen, C. Knabbe, S. Bates, D. Bronzert, K. Huff, and A. Kasid (1987). Growth regulation of human breast carcinoma occurs through regulated growth factor secretion.J. Cell. Biochem. 351–16.

    Article  PubMed  Google Scholar 

  19. R. Clarke, N. Brunner, D. Katz, P. Glanz, R. B. Dickson, M. E. Lippman, and F. G. Kern (1989). The effects of constitutive expression of transforming growth factor-a on the growth of MCF-7 human breast cancer cellsin vitro andin vivo.Mol. Endocrinol. 3372–380.

    PubMed  Google Scholar 

  20. S. E. Bates, N. E. Davidson, E. M. Valverius, C. E. Freter, R. B. Dickson, J. P. Tam, J. E. Kudlow, M. E. Lippman, and D. S. Salomon (1988). Expression of transforming growth factor-alpha and its messenger ribonucleic acid in human breast cancer: Its regulation by estrogen and its possible functional significance.Mol. Endocrinol. 2543–555.

    PubMed  Google Scholar 

  21. S. Nicholson, P. Halcrow, J. R. Farndon, J. R. C. Sainsbury, P. Chambers, and A. L. Harris (1989). Expression of epidermal growth factor receptors associated with lack of response to endocrine therapy in recurrent breast cancer.Lancet.8631182–185.

    Article  Google Scholar 

  22. S. Nicholson, J. Richard, C. Sainsbury, P. Halcrow, P. Kelly, B. Angus, C. Wright, J. Henry, J. R. Farndon, and A. L. Harris (1991). Epidermal growth factor receptor (EGFr)—Results of a six year follow-up study in operable Breast cancer with emphasis on the node negative subgroup.Br. J. Cancer 63146–150.

    PubMed  Google Scholar 

  23. A. L. Harris, S. Nicholson, J. R. C. Sainsbury, J. Farndon, and C. Wright (1989). Epidermal growth factor receptors in breast cancer: Association with early relapse and death, poor response to hormones and interactions withneu.J. Steroid Biochem. 34123–131.

    Article  PubMed  Google Scholar 

  24. M. Kyprianou, H. F. English, N. E. Davidson, and J. T. Isaacs (1991). Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation.Cancer Res. 51162–166.

    PubMed  Google Scholar 

  25. S. A. W. Fuqua, S. D. Fitzgerald, G. C. Chamness, A. K. Tandon, D. P. McDonnell, Z. Nawaz, B. W. O'Malley, and W. L. Mcguire (1991). Variant human breast tumor estrogen receptor with constitutive transcriptional activity.Cancer Res. 51105–109.

    PubMed  Google Scholar 

  26. S. A. W. Fuqua, G. C. Chamness, and W. L. Mcguire (1993). Estrogen receptor mutations in breast cancer.J. Cell Biochem. 51135–139.

    Article  PubMed  Google Scholar 

  27. W. E. Holmes, M. X. Sliwkowski, R. W. Akita, W. J. Henzel, L. J., J. W. Park, D. Yansura, N. Abadi, H. Raab, G. D. Lewis, M. Shepard, W.-J. Kuang, W. I. Wood, D. V. Goeddel, and R. L. Vandlen (1992). Identification of heregulin, a specific activator of p185erb2.Science 2561205–1210.

    PubMed  Google Scholar 

  28. R. Lupu, R. Colomer, B. Kannan, and M. E. Lippman (1992). Characterization of a growth factor that binds exclusively to theerbB-2 receptor and induces cellular responses.Proc. Natl. Acad. Sci. USA 892287–2291.

    PubMed  Google Scholar 

  29. R. Lupu, R. Colomer, G. Zugmaier, J. Sarup, M. Shepard, D. Slamon, and M. E. Lippman (1990). Direct interaction of a ligand for theerbB2 oncogene product with the EGF receptor and p185erbB2.Science 2491552–1555.

    PubMed  Google Scholar 

  30. M. H. Kraus, J. H. Pierce, T. P. Fleming, K. C. Robbins, P. P. DiFiore, and S. A. Aaronson (1988). Mechanisms by which genes encoding growth factors and growth factor receptors contribute to malignant transformation. InMembrane in Cancer Cells, New York Academy of Sciences, New York.

    Google Scholar 

  31. J. Taylor-Papadimitriou, M. Shearer, and M. G. P. Stoker (1977). Growth requirements of human mammary epithelial cells in culture.Int. J. Cancer 20903–908.

    PubMed  Google Scholar 

  32. R. C. Hallowes, R. Millis, D. Pigott, M. Shearer, M. G. P. Stoker, and J. Taylor-Papadimitriou (1977). Results on a pilot study of cultures of human lacteal secretions and benign and malignant breast tumors.Clin. Oncol. 381–90.

    PubMed  Google Scholar 

  33. E. V. Gaffney, F. P. Polanowski, S. E. Blackburn, J. T. Lambiase, and R. E. Burke (1976). Cultures of normal human mammary cells.Cell Differ. 569–81.

    Article  PubMed  Google Scholar 

  34. E. V. Gaffney and D. Pigott (1978). Hydrocortisone stimulation of human mammary epithelial cells.In Vitro 14621–624.

    PubMed  Google Scholar 

  35. J. Taylor-Papadimitriou, M. Shearer, and R. Tilly (1977). Some properties of cells cultured from early-lactation human milk.J. Natl. Cancer Inst. 581563–1571.

    PubMed  Google Scholar 

  36. M. Stampfer, R. C. Hallowes, and A. J. Hackett (1980). Growth of normal human mammary cells in culture.In Vitro 16415–425.

    PubMed  Google Scholar 

  37. H. S. Smith, S. Lan, R. Ceriani, A. J. Hackett, and M. R. Stampfer (1981). Clonal proliferation of cultured nonmalignant and malignant human breast epithelia.Cancer Res. 414637–4643.

    PubMed  Google Scholar 

  38. S. L. Hammond, R. G. Ham, and M. R. Stampfer (1984). Serum-free growth of human mammary epithelial cells: Rapid clonal growth in defined medium and extended serial passage with pituitary extract.Proc. Natl. Acad. Sci. USA 815435–5439.

    PubMed  Google Scholar 

  39. S. P. Ethier (1985). Primary culture and serial passage of normal and carcinogen-treated rat mammary epithelial cellsin vitro.J. Natl. Cancer Inst. 741307–1318.

    PubMed  Google Scholar 

  40. S. P. Ethier (1986). Serum-free culture conditions for the growth of normal rat mammary epithelial cells in primary culture.In Vitro Cell. Dev. Biol. 22485–490.

    PubMed  Google Scholar 

  41. S. P. Ethier, R. M. Summerfelt, K. C. Cundiff, and B. B. Asch (1990). The influence of growth factors on the proliferative potential of normal and primary breast cancer-derived human breast epithelial cells.Breast Cancer Res. Treat. 17221–230.

    Article  Google Scholar 

  42. O. W. Petersen and B. van Deurs (1987). Preservation of defined phenotypic traits in short-term cultured human breast carcinoma derived epithelial cells.Cancer Res. 47856–866.

    PubMed  Google Scholar 

  43. V. Band and R. Sager (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. USA 861249–1253.

    PubMed  Google Scholar 

  44. D. Zajchowski, V. Band, N. Pauzie, A. Tager, M. Stampfer, and R. Sager (1988). Expression of growth factors and oncogenes in normal and tumor-derived human mammary epithelial cells.Cancer Res. 487041–7047.

    PubMed  Google Scholar 

  45. J. Taylor-Papadimitriou, M. Stampfer, J. Barter, A. Lewis, M. Boshell, E. B. Lane, and I. M. Leith (1989). Keratin expression in human mammary cells cultured from normal and malignant tissue: relation toin vivo phenotypes and influence of medium.J. Cell Sci. 94403–413.

    PubMed  Google Scholar 

  46. R. B. Owens, H. S. Smith, W. A. Nelson-Rees, and E. L. Springer (1976). Epithelial cell cultures from normal and cancerous tissues.J. Natl. Cancer Inst. 56843–849.

    PubMed  Google Scholar 

  47. H. S. Smith, A. J. Hacket, J. L. Riggs, M. W. Mosesson, J. R. Walton, and M. R. Stampfer (1979). Properties of epithelial cells cultured from human carcinomas and non-malignant tissues.J. Supramol. Struct. 11147–166.

    Article  PubMed  Google Scholar 

  48. M. R. Stampfer, A. J. Hacket, H. S. Smith, M. C. Hancock, J. P. Leung, and T. S. Edgington (1982). Growth of human mammary epithelium in culture and expression of tumor-specific properties. InGrowth-Cells in Hormonally Defined Media, Cold Spring Harbor, Laboratory, Cold Spring Harbor, New York.

    Google Scholar 

  49. S. R. Wolman, H. S. Smith, M. Stampfer, and A. J. Hackett (1985). Growth of diploid cells from breast cancers.Cancer Genet. Cytogenet. 1649–64.

    Article  PubMed  Google Scholar 

  50. S. P. Ethier, M. L. Mahacek, W. J. Gullick, T. J. Frank, and B. L. Weber (1993). Differential isolation of normal luminal mammary epithelial cells and breast cancer cells from primary and metastatic sites using selective media.Cancer Res. 53627–635.

    PubMed  Google Scholar 

  51. O. W. Petersen, B. van Deurs, K. V. Nielsen, M. W. Madsen, I. Laursen, I. Balslev, and P. Briand (1990). Differential tumorigenicity of two autologous human breast carcinoma cell lines, HMT-3909S1 and HMT-3909S8, established in serum-free medium.Cancer Res. 501257–1270.

    PubMed  Google Scholar 

  52. V. Band, D. Zajchowski, D. Swisshelm, D. Trask, V. Kulesa, C. Cohen, J. Connolly, and R. Sager (1990). Tumor progression in four mammary epithelial cell lines derived from the same patient.Cancer Res. 507351–7357.

    PubMed  Google Scholar 

  53. P. Meltzer, A. Leibovitz, W. Dalton, H. Villar, T. Kute, J. Davis, R. Nagle, and J. Trent (1991). Establishment of two new cell lines derived from human breast carcinomas withHER-2/neu amplification.Br. J. Cancer 63727–735.

    PubMed  Google Scholar 

  54. K. E. Kokeny, C. A. Dilts, and S. E. Ethier (1994).Erb-B family receptor expression and growth regulation in two newly isolated human breast cancer cell lines.Breast Cancer Res. Treat. (submitted).

  55. M. L. Mahacek, D. G. Beer, T. S. Frank, and S. P. Ethier (1993). Finite proliferative lifespanin vitro of a human breast cancer cell strain isolated from a metastatic lymph node.Breast Cancer Rest. Treat. 28267–276.

    Article  Google Scholar 

  56. V. Collins, R. K. Loeffler, and H. Tivey (1956). Observations on growth rates of human tumors.Am. J. Roentgenol. 76988–1000.

    Google Scholar 

  57. J. Gershon-Cohen, S. M. Berger, and H. S. Klickstein (1963). Roentgenography of breast cancer moderating concept of biological predeterminism.Cancer 16961–964.

    PubMed  Google Scholar 

  58. D. V. Fournier, E. Weber, W. Hoeffken,et al. (1980). Growth rate of 147 mammary carcinomas.Cancer 452198–2207.

    PubMed  Google Scholar 

  59. M. R. Stampfer and J. C. Bartley (1985). Induction of transformation and continuous cell lines from normal human mammary epithelial cells after exposure to benzo[a]pyrene.Proc. Natl. Acad. Sci. USA 822394–2398.

    PubMed  Google Scholar 

  60. H. D. Soule, T. M. Malony, S. R. Wolman, W. D. Peterson, R. Brenz, C. M. McGrath, J. Russo, R. J. Pauley, R. F. Jones, and S. C. Brooks (1990). Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10.Cancer Res. 506075–6086.

    PubMed  Google Scholar 

  61. M. W. Madsen, A. E. Lykkesfeldt, I. Laursen, K. V. Nielsen, and P. Briand (1992). Altered gene expression of c-myc, epidermal growth factor receptor, transforming growth factor-a, and c-erb-B2 in an immortalized human breast epithelial cell line, HMT-3522, is associated with decreased growth factor requirements.Cancer Res. 521210–1217.

    PubMed  Google Scholar 

  62. R. Clark, M. R. Stampfer, R. Milley, E. O'Rourke, K. H. Walen, M. Kriegler, J. Kopplin, and F. McCormick (1988). Transformation of human mammary epithelial cells by oncogenic retroviruses.Cancer Res. 484689–4694.

    PubMed  Google Scholar 

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  1. Department of Radiation Oncology, Division of Cancer and Radiation Biology, University of Michigan Medical School, 48109-0582, Ann Arbor, Michigan

    Stephen P. Ethier

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Ethier, S.P. Human breast cancer cell lines as models of growth regulation and disease progression. J Mammary Gland Biol Neoplasia 1, 111–121 (1996). https://doi.org/10.1007/BF02096306

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