MCF-7: the first hormone-responsive breast cancer cell line.

On Thursday,January2, 1997, Dr. HerbertSoule, the scientist who developed the MCF-7 breast cancer cell line, died. At the time, we were in the process of writingthis tributeto markthe 25th anniversary of Dr. Soule's remarkableaccomplishment.The cells, derived from a breast cancer patient in the Detroit area and developed at the Michigan CancerFoundation,Detroit,became a standardmodel in hundredsof laboratories around the world. In retrospect, the story of the diverse uses of these cells is really the history of our developing knowledge of hormone-regulatedcell replication, and they provided a unique insight into the endocrine therapyof breastcancer. Our article is offered as a tributeand memorial to Dr. Soule. We will trace researchwith MCF-7 cells to illustratethe change in our ideas about cell replication and to highlight the advances in our understanding of the signal transduction pathway of estrogen and the molecular biology of estrogen action. All of these advances depended on the uniquepropertiesof MCF-7 cells. Additionally,it is important to appreciate that the cell system has now found applications in experimental therapeutics, and the results from these studies are being translated to the clinic for the treatment of patients. None of this would have been possible withoutDr. Soule's skill as a cell biologist.

[1]  P. Chambon,et al.  Functional domains of the human estrogen receptor , 1987, Cell.

[2]  P. Chambon,et al.  Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. , 1982, Nucleic acids research.

[3]  H. Rochefort,et al.  Autocrine growth stimulation of the MCF 7 breast cancer cells by the estrogen-regulated 52 K protein. , 1986, Endocrinology.

[4]  P. Argos,et al.  Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A , 1986, Nature.

[5]  E. Jensen,et al.  Binding of antiestrogens exposes an occult antigenic determinant in the human estrogen receptor. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[6]  H. Soule,et al.  Estrogen receptor in a human cell line (MCF-7) from breast carcinoma. , 1973, The Journal of biological chemistry.

[7]  S. Masood Immunocytochemical localization of estrogen and progesterone receptors in imprint preparations of breast carcinomas , 1992, Cancer.

[8]  G. Greene,et al.  Monoclonal antibodies localize oestrogen receptor in the nuclei of target cells , 1984, Nature.

[9]  J. Katzenellenbogen,et al.  Bis(4-hydroxyphenyl)[2-(phenoxysulfonyl)phenyl]methane: isolation and structure elucidation of a novel estrogen from commercial preparations of phenol red (phenolsulfonphthalein) , 1988, Journal of medicinal chemistry.

[10]  W. McGuire,et al.  Predicting response to endocrine therapy in human breast cancer: a hypothesis. , 1975, Science.

[11]  M. Stampfer,et al.  Modulation by estrogen and growth factors of transforming growth factor-alpha and epidermal growth factor receptor expression in normal and malignant human mammary epithelial cells. , 1989, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[12]  S. Robinson,et al.  Implications of tamoxifen metabolism in the athymic mouse for the study of antitumor effects upon human breast cancer xenografts. , 1989, European journal of cancer & clinical oncology.

[13]  M. Blankenstein,et al.  Mitogenic stimulation of human breast cancer cells in a growth factor‐defined medium: Synergistic action of insulin and estrogen , 1988, Journal of cellular physiology.

[14]  B. Katzenellenbogen,et al.  Human estrogen receptor ligand activity inversion mutants: receptors that interpret antiestrogens as estrogens and estrogens as antiestrogens and discriminate among different antiestrogens. , 1996, Molecular endocrinology.

[15]  G. Greene,et al.  Selection and characterization of a breast cancer cell line resistant to the antiestrogen LY 117018. , 1985, Endocrinology.

[16]  J. Pink,et al.  An estrogen-independent MCF-7 breast cancer cell line which contains a novel 80-kilodalton estrogen receptor-related protein. , 1995, Cancer research.

[17]  V. Jordan,et al.  Nuclear [3H]4-hydroxytamoxifen (4-OHTAM)- and [3H]estradiol (E2)-estrogen receptor complexes in the MCF-7 breast cancer and GH3 pituitary tumor cell lines , 1984, Molecular and Cellular Endocrinology.

[18]  ADJUVANT TAMOXIFEN IN THE MANAGEMENT OF OPERABLE BREAST CANCER: THE SCOTTISH TRIAL Report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh , 1987, The Lancet.

[19]  H. Soule,et al.  Characterization of epithelial phenotypes in mortal and immortal human breast cells , 1992, International journal of cancer.

[20]  M. Lippman,et al.  The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. , 1976, Cancer research.

[21]  Chawnshang Chang,et al.  An estrogen receptor positive MCF-7 clone that is resistant to antiestrogens and estradiol , 1992, Molecular and Cellular Endocrinology.

[22]  A. Wakeling,et al.  Steroidal pure antioestrogens. , 1987, The Journal of endocrinology.

[23]  E. Gelmann,et al.  Use of two MCF-7 cell variants to evaluate the growth regulatory potential of estrogen-induced products. , 1986, Cancer research.

[24]  Human estrogen receptor ligand activity inversion mutants: receptors that interpret antiestrogens as estrogens and estrogens as antiestrogens and discriminate among different antiestrogens. , 1996, Molecular endocrinology.

[25]  B. Katzenellenbogen,et al.  Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. , 1987, Cancer research.

[26]  C. Milstein,et al.  Continuous cultures of fused cells secreting antibody of predefined specificity , 1975, Nature.

[27]  J. Rygaard,et al.  Heterotransplantation of a human malignant tumour to "Nude" mice. , 2009, Acta pathologica et microbiologica Scandinavica.

[28]  P. Chambon,et al.  Activation of pS2 gene transcription is a primary response to estrogen in the human breast cancer cell line MCF-7. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[29]  E. Dodds,et al.  Synthetic Œstrogenic Agents without the Phenanthrene Nucleus , 1936, Nature.

[30]  V. Jordan,et al.  The role of estrogen receptor mutations in tamoxifen-stimulated breast cancer , 1997, The Journal of Steroid Biochemistry and Molecular Biology.

[31]  C Sonnenschein,et al.  The role of estrogens on the proliferation of human breast tumor cells (MCF-7). , 1985, Journal of steroid biochemistry.

[32]  Jamel Chelly,et al.  Transcription of the dystrophin gene in human muscle and non-muscle tissues , 1988, Nature.

[33]  W. McGuire,et al.  Estrogen receptor. Unoccupied sites in nuclei of a breast tumor cell line. , 1977, The Journal of biological chemistry.

[34]  J. Russo,et al.  Ultrastructural and immunocytochemical characterization of an immortalized human breast epithelial cell line, MCF-10. , 1990, Cancer research.

[35]  E. Gelmann,et al.  Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[36]  C. Osborne,et al.  Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic nude mice. , 1985, Cancer research.

[37]  T. Thorsen,et al.  Oestradiol treatment increases the sensitivity of MCF-7 cells for the growth stimulatory effect of IGF-I , 1992, The Journal of Steroid Biochemistry and Molecular Biology.

[38]  P. Chambon,et al.  Cloning of the human estrogen receptor cDNA. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[39]  E. Gelmann,et al.  Epidermal growth factor receptor gene expression in estrogen receptor-positive and negative human breast cancer cell lines. , 1987, Molecular endocrinology.

[40]  V. Jordan,et al.  Transfection of human estrogen receptor (ER) cDNA into ER-negative mammalian cell lines , 1994, The Journal of Steroid Biochemistry and Molecular Biology.

[41]  S. Robinson,et al.  Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: a model to study the tumoristatic action of tamoxifen. , 1988, Journal of steroid biochemistry.

[42]  G. Greene,et al.  Monoclonal antibodies to estrophilin: probes for the study of estrogen receptors. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[43]  A. Long,et al.  A human cell line from a pleural effusion derived from a breast carcinoma. , 1973, Journal of the National Cancer Institute.

[44]  C. Sonnenschein,et al.  But ... are estrogens per se growth-promoting hormones? , 1980, Journal of the National Cancer Institute.

[45]  C. Osborne,et al.  Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase. , 1983, Cancer research.

[46]  T. Maloney,et al.  Evidence for a direct growth-stimulating effect of estradiol on human MCF-7 cells in vivo. , 1984, Cancer research.

[47]  W. Welshons,et al.  Adaptation of estrogen-dependent MCF-7 cells to low estrogen (phenol red-free) culture. , 1987, European journal of cancer & clinical oncology.

[48]  J. Robertson,et al.  Oestrogen receptor: a stable phenotype in breast cancer. , 1996, British Journal of Cancer.

[49]  B. Katzenellenbogen,et al.  Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[50]  C. Osborne,et al.  Acquired tamoxifen resistance: correlation with reduced breast tumor levels of tamoxifen and isomerization of trans-4-hydroxytamoxifen. , 1991, Journal of the National Cancer Institute.

[51]  E. M. Pantelouris,et al.  Absence of Thymus in a Mouse Mutant , 1968, Nature.

[52]  E. Jensen,et al.  A two-step mechanism for the interaction of estradiol with rat uterus. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[53]  P. Chambon,et al.  Promoter elements of genes coding for proteins and modulation of transcription by estrogens and progesterone. , 1984, Recent progress in hormone research.

[54]  D. Rea,et al.  Effects of an exon 5 variant of the estrogen receptor in MCF-7 breast cancer cells. , 1996, Cancer research.

[55]  D. Heitjan,et al.  Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. , 1995, The Journal of clinical endocrinology and metabolism.

[56]  P. Chambon,et al.  The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. , 1989, The EMBO journal.

[57]  D. Kaufman,et al.  Multihormonal regulation of insulin-like growth factor-I-related protein in MCF-7 human breast cancer cells. , 1988, Molecular endocrinology.

[58]  W. Welshons,et al.  Estrogenic activity of phenol red , 1988, Molecular and Cellular Endocrinology.

[59]  J. Shine,et al.  Sequence and expression of human estrogen receptor complementary DNA. , 1986, Science.

[60]  W. McGuire,et al.  Nuclear mechanisms of estrogen action. Effects of estradiol and anti-estrogens on estrogen receptors and nuclear receptor processing. , 1978, The Journal of biological chemistry.

[61]  J. Gorski,et al.  A receptor molecule for estrogens: studies using a cell-free system. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[62]  M. Mattei,et al.  Cloning and sequencing of the 52K cathepsin D complementary deoxyribonucleic acid of MCF7 breast cancer cells and mapping on chromosome 11. , 1988, Molecular endocrinology.

[63]  S. Thorpe,et al.  Quantitative immunological detection of estrogen receptors in nuclear pellets from human breast cancer biopsies. , 1986, Cancer research.

[64]  M. Lippman,et al.  Isolation and characterization of a tamoxifen-resistant cell line derived from MCF-7 human breast cancer cells. , 1981, The Journal of biological chemistry.

[65]  B. Katzenellenbogen,et al.  Lipophilic impurities, not phenolsulfonphthalein, account for the estrogenic activity in commercial preparations of phenol red. , 1988, Journal of steroid biochemistry.

[66]  M. Lippman,et al.  Effects of estrone, estradiol, and estriol on hormone-responsive human breast cancer in long-term tissue culture. , 1977, Cancer research.

[67]  D. Yee,et al.  Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer. , 1989, Molecular endocrinology.

[68]  J. Pink,et al.  Models of estrogen receptor regulation by estrogens and antiestrogens in breast cancer cell lines. , 1996, Cancer research.

[69]  M. Lippman,et al.  Oestrogen-responsive human breast cancer in long term tissue culture , 1975, Nature.

[70]  W. McGuire,et al.  MCF-7: A human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors , 1975, Steroids.

[71]  M. Parker,et al.  Antiestrogen ICI 164,384 reduces cellular estrogen receptor content by increasing its turnover. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[72]  S. O’Brien,et al.  Clonal variation of MCF-7 breast cancer cells in vitro and in athymic nude mice. , 1983, Cancer research.

[73]  R. Noble,et al.  BIOLOGICAL EFFECTS OF THE SYNTHETIC ŒSTROGENIC SUBSTANCE 4 : 4'-DIHYDROXY-α : β-DIETHYLSTILBENE , 1938 .

[74]  J. Field,et al.  Serum regulation of the estrogen responsiveness of the human breast cancer cell line MCF-7. , 1983, Cancer research.

[75]  V. Jordan,et al.  Hormone receptor assays: clinical usefulness in the management of carcinoma of the breast. , 1988, Critical reviews in clinical laboratory sciences.

[76]  G. Beatson On the Treatment of Inoperable Cases of Carcinoma of the Mamma: Suggestions for a New Method of Treatment, with Illustrative Cases , 1896, Transactions. Medico-Chirurgical Society of Edinburgh.

[77]  C. Welsch Host factors affecting the growth of carcinogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins. , 1985, Cancer research.

[78]  W. McGuire,et al.  Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. , 1978, The Journal of biological chemistry.

[79]  W. McGuire,et al.  Hormone Dependent Breast Cancer , 1989 .

[80]  W. McGuire,et al.  Estrogen control of progesterone receptor in human breast cancer: role of estradiol and antiestrogen. , 1978, Endocrinology.

[81]  V. Jordan,et al.  Inhibition of tamoxifen-stimulated growth of an MCF-7 tumor variant in athymic mice by novel steroidal antiestrogens. , 1989, Cancer research.

[82]  Kenneth P. Karey,et al.  Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17 beta-estradiol. , 1988, Cancer research.

[83]  V. Jordan,et al.  Should adjuvant tamoxifen therapy be stopped at 5 years? , 1996, The cancer journal from Scientific American.

[84]  F. Miller,et al.  MCF10AT: a model for the evolution of cancer from proliferative breast disease. , 1996, The American journal of pathology.

[85]  C. Osborne,et al.  Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice. , 1989, The Journal of clinical investigation.

[86]  D. Wilson,et al.  Demonstration of insulin-like growth factor (IGF-I and -II) receptors and binding protein in human breast cancer cell lines. , 1988, Biochemical and biophysical research communications.

[87]  V. Jordan,et al.  Development of tamoxifen-stimulated growth of MCF-7 tumors in athymic mice after long-term antiestrogen administration. , 1988, Cancer research.

[88]  Point mutation of estrogen receptor (ER) in the ligand-binding domain changes the pharmacology of antiestrogens in ER-negative breast cancer cells stably expressing complementary DNAs for ER. , 1992, Molecular endocrinology.

[89]  W. Welshons,et al.  Estrogen receptor distribution in enucleated breast cancer cell lines. , 1988, Endocrinology.

[90]  P. Chambon,et al.  Characterization of the estrogen receptor in two antiestrogen-resistant cell lines, LY2 and T47D. , 1990, Cancer research.

[91]  V. Jordan,et al.  Endocrine pharmacology of antiestrogens as antitumor agents. , 1990, Endocrine reviews.

[92]  I W Taylor,et al.  Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau-phase cells. , 1983, Cancer research.

[93]  J. Gorski,et al.  A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[94]  F. Miller,et al.  Xenograft model of progressive human proliferative breast disease. , 1993, Journal of the National Cancer Institute.

[95]  R. Dickson,et al.  Estrogen-induced factors of breast cancer cells partially replace estrogen to promote tumor growth. , 1986, Science.

[96]  A. Howell,et al.  Response after withdrawal of tamoxifen and progestogens in advanced breast cancer. , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[97]  S. Hilsenbeck,et al.  Comparison of the effects of a pure steroidal antiestrogen with those of tamoxifen in a model of human breast cancer. , 1995, Journal of the National Cancer Institute.

[98]  E. Borden,et al.  Differential ability of antiestrogens to stimulate breast cancer cell (MCF-7) growth in vivo and in vitro. , 1989, Cancer research.

[99]  C. Osborne,et al.  Human breast cancer in the athymic nude mouse: cytostatic effects of long-term antiestrogen therapy. , 1987, European journal of cancer & clinical oncology.

[100]  D. Wolf,et al.  Investigation of the mechanism of tamoxifen-stimulated breast tumor growth with nonisomerizable analogues of tamoxifen and metabolites. , 1993, Journal of the National Cancer Institute.

[101]  F. Grantham,et al.  Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic nude mice. , 1981, Journal of the National Cancer Institute.

[102]  A. Howell,et al.  Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. , 1996, British Journal of Cancer.

[103]  C. Nolan,et al.  Monoclonal antibodies to human estrogen receptor. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[104]  Predicting response to endocrine therapy in human breast cancer: a hypothesis. , 1976, Science.

[105]  P. Briand,et al.  Estrogen receptor messenger RNA splice variants are not involved in antiestrogen resistance in sublines of MCF-7 human breast cancer cells. , 1997, Cancer research.

[106]  Ulrich Pfeffer,et al.  Coexpression of multiple estrogen receptor variant messenger RNAs in normal and neoplastic breast tissues and in MCF-7 cells. , 1995, Cancer research.

[107]  G. Greene,et al.  Antibodies to estrogen receptor: immunochemical similarity of estrophilin from various mammalian species. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[108]  S. Shafie Erratum: Estrogen and the Growth of Breast Cancer: New Evidence Suggests Indirect Action , 1980, Science.

[109]  V. Jordan,et al.  Determination of estrogen receptor in breast cancer using monoclonal antibody technology: results of a multicenter study in the United States. , 1986, Cancer research.

[110]  W. Sly,et al.  Insulin-like growth factor receptor expression and function in human breast cancer. , 1990, Cancer research.

[111]  G. Greene,et al.  Antibodies to estrophilin: comparison between rabbit and goat antisera. , 1979, Journal of steroid biochemistry.

[112]  B. Pau,et al.  Characterization of monoclonal antibodies to the estrogen-regulated Mr 52,000 glycoprotein and their use in MCF7 cells. , 1985, Cancer research.

[113]  M. Johnson,et al.  Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. , 1990, The Journal of biological chemistry.

[114]  G. Sato,et al.  Growth of a human mammary tumour cell line in a serum-free medium , 1979, Nature.

[115]  P. Satyaswaroop,et al.  Estrogen-like effects of tamoxifen on human endometrial carcinoma transplanted into nude mice. , 1984, Cancer research.

[116]  D. Wilson,et al.  Characterization of insulin-like growth factor binding proteins from human breast cancer cells. , 1989, Molecular endocrinology.

[117]  I. Taylor,et al.  Tamoxifen induces accumulation of MCF 7 human mammary carcinoma cells in the G0/G1 phase of the cell cycle. , 1983, European journal of cancer & clinical oncology.

[118]  W. McGuire,et al.  Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[119]  R Clarke,et al.  Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[120]  K. Pollow,et al.  Comparison of immunocytochemical estrogen receptor assay, estrogen receptor enzyme immunoassay, and radioligand-labeled estrogen receptor assay in human breast cancer and uterine tissue. , 1986, Cancer research.

[121]  M. Boylan,et al.  Changes in insulin-like growth factor-I receptor expression and binding protein secretion associated with tamoxifen resistance and estrogen independence in human breast cancer cells in vitro. , 1996, Cancer letters.

[122]  B. Katzenellenbogen,et al.  Differential regulation of gene expression by estrogen in estrogen growth-independent and -dependent MCF-7 human breast cancer cell sublines. , 1991, Molecular endocrinology.

[123]  R. Derynck,et al.  Evidence that transforming growth factor-β is a hormonally regulated negative growth factor in human breast cancer cells , 1987, Cell.

[124]  B. Giovanella,et al.  Heterotransplantation of human malignant tumors in "nude" thymusless mice. II. Malignant tumors induced by injection of cell cultures derived from human solid tumors. , 1974, Journal of the National Cancer Institute.

[125]  J. Pink,et al.  A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7. , 1996, Nucleic acids research.

[126]  R. Furlanetto,et al.  Somatomedin-C receptors and growth effects in human breast cells maintained in long-term tissue culture. , 1984, Cancer research.

[127]  V. Jordan Estrogen/Antiestrogen Action and Breast Cancer Therapy , 1986 .

[128]  I. Todd,et al.  A New Anti-oestrogenic Agent in Late Breast Cancer: An Early Clinical Appraisal of ICI46474 , 1971, British Journal of Cancer.

[129]  H. Rochefort,et al.  A secreted glycoprotein induced by estrogen in human breast cancer cell lines , 1980, Cell.

[130]  J. Gorski,et al.  Nuclear localization of unoccupied oestrogen receptors , 1984, Nature.

[131]  P. Chambon,et al.  Genomic organization of the human oestrogen receptor gene. , 1988, The EMBO journal.

[132]  C. Osborne,et al.  Human breast cancer cell cycle synchronization by estrogens and antiestrogens in culture. , 1984, Cancer research.

[133]  D. Kaufman,et al.  Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. , 1986, Cancer research.

[134]  H. Soule,et al.  Estrogen responsive proliferation of clonal human breast carcinoma cells in athymic mice. , 1980, Cancer letters.

[135]  B. Katzenellenbogen,et al.  Response-specific antiestrogen resistance in a newly characterized MCF-7 human breast cancer cell line resulting from long-term exposure to trans-hydroxytamoxifen , 1996, The Journal of Steroid Biochemistry and Molecular Biology.

[136]  W. McGuire,et al.  Tamoxifen and the isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.