Hormone Action in Human Breast Cancer Estrogen Regulation of Specific Proteins

  • David J. Adams
  • Dean P. Edwards
  • William L. McGuire
Part of the Biochemical Endocrinology book series (BIOEND)


How do estrogens regulate mammary tumor growth and function? Researchers have been pondering this question ever since breast tumor regression was reported in premenopausal patients following oophorectomy (Beatson, 1896). However, systematic exploitation of endocrine ablative surgery did not occur until the 1950s when Huggins and Dao (1954) obtained 38 clinical remissions after performing 100 ovariectomies for palliation of advanced breast cancer. A similar result occurred with adrenalectomy (Huggins and Bergenstal, 1952) and patients responding to this surgery were found to concentrate [3H]hexestrol in their metastases (Folca et al., 1961). Jensen et al. (1967) and Terenius (1968) then observed that the clinical response to endocrine therapy was correlated with specific binding of estradiol by certain human breast tumor biopsy specimens. This observation and the discovery of a high-affinity receptor protein for estradiol in the cytoplasm of target cells (loft and Gorski, 1966) led to the widespread use of an estrogen receptor (ER) assay to identify hormone-responsive breast tumors (McGuire et al., 1975). Subsequent studies have shown that approximately two-thirds of all breast tumor biopsy specimens contain estrogen receptors, and, of these tumors, that about half respond to ablative and additive endocrine therapies (Edwards et al., 1979). Furthermore, ER analysis of the primary tumor can predict response to endocrine therapy if inaccessible metastatic disease develops.


Estrogen Receptor Breast Tumor Progesterone Receptor Estrogen Action Human Breast Cancer Cell Line 
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  1. Adams, D. J., Edwards, D. P., and McGuire, W. L., 1980, Estrogen regulation of specific messenger RNAs in human breast cancer cells, Biochem. Biophys. Res. Commun. 97: 1354.CrossRefGoogle Scholar
  2. Allegra, J. C., and Lippman, M. E., 1978, Growth of a human breast cancer cell line in serumfree hormone-supplemented medium, Cancer Res. 38: 3823.PubMedGoogle Scholar
  3. Baker, H. J., and Shapiro, D. J., 1977, Kinetics of estrogen induction of Xenopus laevis vitellogenin messenger RNA as measured by hybridization to complementary DNA, J. Biol. Chem. 252: 8428.Google Scholar
  4. Barker, K. L., Adams, D. J., and Donohue, T. M., 1981, Regulation of the levels of mRNA for glucose-6-phosphate dehydrogenase and its rate of translation in the uterus by estradiol, in: Cellular and Molecular Mechanisms of Implantation ( S. Glasser and D. Bullock, eds.), pp. 269–281, Plenum Press, New York.CrossRefGoogle Scholar
  5. Barnes, D., 1980, Factors that stimulate proliferation of breast cancer cells in vitro in serum-free medium, in: Cell Biology of Breast Cancer ( C. McGrath, M. Brennan, and M. Rich, eds.), pp. 227–287, Academic Press, New York.Google Scholar
  6. Barnes, D., and Sato, G., 1979, Growth of a human mammary tumor cell line in a serum-free medium, Nature 281: 388.PubMedCrossRefGoogle Scholar
  7. Barnes, D., and Sato, G., 1980, Serum-free cell culture: A unifying approach, Cell 22:649. Baulieu, E. E., Alberga, A., Raynaud-Jammet, C., and Wira, C. R., 1972, New look at the very early steps of oestrogen action in uterus, Nature New Biol. 236: 236.Google Scholar
  8. Beatson, G. T., 1896, On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment, with illustrative cases, Lancet 2: 104.CrossRefGoogle Scholar
  9. Bolander, F. F., Jr., and Topper, Y. J., 1979, Stimulation of lactose synthetase activity and casein synthesis in mouse mammary explants by estradiol, Endocrinology 106: 490.CrossRefGoogle Scholar
  10. Bronzen, D. A., Monaco, M. E., Pinkus, L., Aitken, S., and Lippman, M. E., 1981, Purification and properties of estrogen-responsive cytoplasmic thymidine kinase from human breast cancer, Cancer Res. 41: 604.Google Scholar
  11. Burke, R. E., Harris, S. C., and McGuire, W. L., 1978, Lactate dehydrogenase in estrogen-responsive human breast cancer cells, Cancer Res. 38: 2773.PubMedGoogle Scholar
  12. Busch, H., Gyorkey, F., Busch, R. K., Davis, F. M., Gyorkey, R., and Smetna, A., 1979, A nucleolar antigen found in a broad range of human malignant tumor specimens, Cancer Res. 39: 3024.PubMedGoogle Scholar
  13. Butler, W. B., Kirkland, W. L., and Jorgensen, T. L., 1979, Induction of plasminogen activator by estrogen in a human breast cancer cell line (MCF-7), Biochem. Biophys. Res. Commun. 90: 1328.CrossRefGoogle Scholar
  14. Chambon, P., Benoist, C., Breathnach, R., Cochet, M., Gannon, F., Gerlinger, P., ‘Crust, A., Lemeur, M., LePennec, J. P., Mandel, J. L., O’Hare, K. U., and Perrin, F., 1979, Structural organization and expression of ovalbumin and related chicken genes, in: From Gene to Protein: Information Transfer in Normal and Abnormal Cells ( T. R. Russell, K. Brew, H. Faber, and J. Schultz, eds.), pp. 55–83, Academic Press, New York.Google Scholar
  15. Chan, L., and O’Malley, B. W., 1976, Mechanism of action of the sex steroid hormones, N. Engl. J. Med. 294: 1322.CrossRefGoogle Scholar
  16. Chan, P.-K., Feyerabend, A., Busch, R. K., and Busch, H., 1980, Identification and partial purification of human tumor nucleolar antigen 54/6.3, Cancer Res. 40: 3194.PubMedGoogle Scholar
  17. Crawford, L. V., Pim, D. C., Gurney, E. G., Goodfellow, P., and Taylor-Papadimitriou, J., 1981, Detection of a common feature in several human tumor cell lines—a 53,000 dalton protein, Proc. Natl. Acad. Sci. U.S.A. 78: 41.PubMedCrossRefGoogle Scholar
  18. Cunningham, D. D., Carney, D. H., and Glenn, K. C., 1979, A cell-surface component involved in thrombin-stimulated cell division, in: Hormones and Cell Culture, Book A ( G. H. Sato and R. Ross, eds.), pp. 199–218, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  19. Deeley, R. G., Gordon, J. I., Burns, A. T. H., Mullinix, K. P., Bina-Stein, M., and Goldberger, R. F., 1977, Primary activation of the vitellogenin gene in the rooster, J. Biol. Chem. 252: 8310.PubMedGoogle Scholar
  20. Dippold, W. G., Jay, G., DeLeo, A. B., Khoury, G., and Old, L. J., 1981, p53 Transformation-related protein: Detection by monoclonal antibody in mouse and human cells, Proc. Natl. Acad. Sci. U.S.A. 78: 1695.Google Scholar
  21. Edwards, D. P., Chamness, G. C., and McGuire, W. L., 1979, Estrogen and progesterone receptor proteins in breast cancer, Biochim. Biophys. Acta 560: 457.Google Scholar
  22. Edwards, D. P., Adams, D. J., and McGuire, W. L., 1980a, Estrogen induced synthesis of specific proteins in human breast cancer cells, Biochem. Biophys. Res. Commun. 93: 804.CrossRefGoogle Scholar
  23. Edwards, D. P., Murthy, S. R., and McGuire, W. L., 1980b, Effects of estrogen and antiestrogen on DNA polymerase in human breast cancer, Cancer Res. 40: 1722.PubMedGoogle Scholar
  24. Edwards, D. P., Adams, D. J., and McGuire, W. L., 1981, Estradiol stimulated synthesis of a major intracellular protein in human breast cancer cells (MCF-7), Breast Cancer Treat. Res. 1: 209.Google Scholar
  25. Folca, P. J., Glascock, R. F., and Irvine, W. T., 1961, Studies with tritium-labeled hexestrol in advanced breast cancer, Lancet 2: 796.PubMedCrossRefGoogle Scholar
  26. Goldman, R. D., Kaplan, N. O., and Hall, T. C., 1964, Lactate dehydrogenase in human neoplastic tissues, Cancer Res. 24: 389.PubMedGoogle Scholar
  27. Gospodarowicz, D., Vlodaysky, I., Greenburg, G., and Johnson, L. K., 1979, Cellular shape is determined by the extracellular matrix and is responsible for the control of cellular growth and function, in: Hormones and Cell Culture, Book B ( G. H. Sato and R. Ross, eds.), pp. 561–592, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  28. Haagensen, D. E., Mazoujian, G., Dilley, W. G., Pedersen, C. E., Kister, S. J., and Wells, S. A., 1979, Breast gross cystic disease fluid analysis. I. Isolation and radioimmunoassay for a major component protein, J. Natl. Cancer Inst. 62: 239.Google Scholar
  29. Hakim, A. A., 1980, Estradiol-induced biochemical changes in human neoplastic cells: Estradiolmediated protease, Cancer Biochem. Biophys. 4: 173.Google Scholar
  30. Hilf, R., Rector, W. D., and Orlando, R. A., 1976, Multiple molecular forms of lactate dehydrogenase and glucose 6-phosphate dehydrogenase in hormonal and abnormal human breast tissues, Cancer 37: 1825.PubMedCrossRefGoogle Scholar
  31. Homebeck, W., Brechemier, D., Belton, G., Adnet, J. J., and Robert, L., 1980, Biological significance of elastase-like enzymes in arteriosclerosis and human breast cancer, in: Proteinases and Tumor Invasion ( A. J. Barrett, A. Baici, and P. Strauli, eds.), pp. 117–141, Raven Press, New York.Google Scholar
  32. Horwitz, K. B., and McGuire, W. L., 1977a, Estrogen control of progesterone receptor in human breast cancer, J. Biol. Chem. 253: 2223.Google Scholar
  33. Horwitz, K. B., and McGuire, W. L., 1977b, Progesterone and progesterone receptors in experimental breast cancer, Cancer Res. 37: 1733.PubMedGoogle Scholar
  34. Horwitz, K. B., and McGuire, W. L., 1978, Nuclear mechanisms of estrogen action: Effects of estradiol and antiestrogens on estrogen receptors and nuclear receptor processing, J. Biol. Chem. 253: 8185.PubMedGoogle Scholar
  35. Horwitz, K. B., McGuire, W. L., Pearson, O. H., and Segaloff, A., 1975, Predicting response to endocrine therapy in human breast cancer, Science 189: 726.PubMedCrossRefGoogle Scholar
  36. Horwitz, K. B., Zava, D. T., Thilagar, A. K., Jensen, E. M., and McGuire, W. L., 1978, Steroid receptor analyses of nine human breast cancer cell lines, Cancer Res. 38: 2434.PubMedGoogle Scholar
  37. Horwitz, K. B., Aiginger, P., Kuttenn, F., and McGuire, W. L., 1981, Nuclear estrogen receptor release from antiestrogen suppression: Amplified induction of progesterone receptor in MCF7 human breast cancer cells, Endocrinology 108: 1703.PubMedCrossRefGoogle Scholar
  38. Huggins, C., and Bergenstal, D. M., 1951, Inhibition of human mammary and prostatic cancers by adrenalectomy, Cancer Res. 12: 134.Google Scholar
  39. Huggins, C., and Dao, T. L.-Y., 1954, Characteristics of adrenal-dependent mammary cancers, Ann. Surg. 140: 497.PubMedCrossRefGoogle Scholar
  40. Ip, M., Milholland, R. J., and Rosen, F., 1979, Mammary cancer: Selective action of the estrogen receptor complex, Science 203: 361.PubMedCrossRefGoogle Scholar
  41. Ivarie, R. D., and O’Farrell, P. H., 1978, The glucocorticoid domain: steroid-mediated changes in the rate of synthesis of rat hepatoma proteins, Cell 13: 41.PubMedCrossRefGoogle Scholar
  42. Jay, G., Khoury, G., DeLeo, A. B., Dippold, W. G., and Old, L. J., 1981, p53 Transformation-related protein: Detection of an associated phosphotransferase activity, Proc. Natl. Acad. Sci. U.S.A. 78: 2932.Google Scholar
  43. Jensen, E. V., 1981, Hormone dependency of breast cancer, Cancer 47: 23:19.PubMedCrossRefGoogle Scholar
  44. Jensen, E. V., DeSombre, E. R., and Jungblut, P. W., 1967, Estrogen receptors in hormone-responsive tissues and tumors, in: Endogenous Factors Influencing Host—Tumor Balance ( R. W. Wissler, T. L. Dao, and S. Wood, Jr., eds.), pp. 15–30, University of Chicago Press, Chicago.Google Scholar
  45. Kaye, A. M., and Reiss, N., 1980, The uterine “estrogen induced protein” (IP): Purification, distribution and possible function, in: Steroid Induced Uterine Proteins ( M. Beato, ed.), pp. 3–19, Elsevier/North-Holland Biomedical Press, New York.Google Scholar
  46. Kaye, A. M., Reiss, N., Iacobelli, S., Bartoccioni, E., and Marchetti, P., 1980, The “estrogen-induced protein” in normal and neoplastic cells, in: Hormones and Cancer ( S. Iacobelli, H. R. Lindner, R. J. B. Kino, and M. E. Lippman, eds.), pp. 41–51, Raven Press, New York.Google Scholar
  47. King, R. J. B., 1979, How important are steroids in regulating the growth of mammary tumors?, in: Biochemical Actions of Hormones, Vol. VI, pp. 247–264, Academic Press, New York.Google Scholar
  48. Knight, W. A., Livingston, R. B., Gregory, E. J., and McGuire, W. L., 1977, Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer, Cancer Res. 37: 4669.PubMedGoogle Scholar
  49. Kohler, G., Milstein, C., 1975, Derivation of specific antibody-producing and tumor cell lines by cell fusion, Eur. J. Immunol. 6: 511.CrossRefGoogle Scholar
  50. Leung, C. K. H., and Shiu, R. P. C., 1981, Required presence of both estrogen and pituitary factors for the growth of human breast cancer cells in athymic nude mice, Cancer Res. 41: 546.PubMedGoogle Scholar
  51. Lxkwood, D. H., Boytovich, A. E., Stockdale, F. E., and Topper, Y. J., 1967, Insulin-dependent DNA polymerase and DNA synthesis in mammary epithelial cells in vitro, Proc. Natl. Acad. Sci. U.S.A. 58: 658.CrossRefGoogle Scholar
  52. Mairesse, N., Devleeschouwer, N., Leclercq, G., and Galand, P., 1980, Estrogen-induced protein in the human breast cancer cell line MCF-7, Biochem. Biophys. Res. Commun. 97: 1251.CrossRefGoogle Scholar
  53. Mairesse, N., Devleeschouwer, N., Leclercq, G., and Galand, P., 1981, Estrogen-induced protein in the human breast cancer cell line MCF-7: Further characterization. Fifth International Symposium of the Journal of Steroid Biochemistry, Puerto Vallarta, Jalisco, Mexico.Google Scholar
  54. Martin, T. J., Findlay, D. M., MacIntyre, I., Eisman, J. A., Michelangeli, V. P., Moseley, J. M., and Partridge, N. C., 1980, Calcitonin receptors in a cloned human breast cancer cell line (MCF-7), Biochem. Biophys. Res. Commun. 96: 150.CrossRefGoogle Scholar
  55. McGuire, W. L., Carbone, P. P., Sears, M. E., and Escher, G. C., 1975, Estrogen receptors in human breast cancer: An overview, in: Estrogen Receptors in Human Breast Cancer ( W. L. McGuire, P. P. Carbone, and E. P. Vollmer, eds.), pp. 1–7, Raven Press, New York.Google Scholar
  56. McKnight, S. G., and Palmiter, R. D., 1979, Transcriptional regulation of the ovalbumin and conalbumin genes by steroid hormones in the chick oviduct. J. Biol. Chem. 254: 9050.PubMedGoogle Scholar
  57. Miller, L. K., Tuazon, F. B., Niu, E.-M., and Sherman, M. R., 1981, Human breast tumor estrogen receptor: Effects of molybdate and electrophoretic analyses, Endocrinology 108: 1369.PubMedCrossRefGoogle Scholar
  58. Milner, J, and McCormick, F., 1980, Lymphocyte stimulation: Concanavalin A induces the expression of a 53K protein, Cell Biol. lnt. Rep. 4: 663.Google Scholar
  59. Namer, M., LaIanne, C., and Baulieu, E. E., 1980, Increase of progesterone receptor by tamoxifen as a hormonal challenge test in breast cancer, Cancer Res. 40: 1750.PubMedGoogle Scholar
  60. Notides, A., and Gorski, J., 1966, Estrogen-induced synthesis of a specific uterine protein, Proc. Natl. Acad. Sci. U.S.A. 56: 230.PubMedCrossRefGoogle Scholar
  61. O’Farrell, P. J., 1975, High resolution two-dimensional electrophoresis of proteins, J. Biol. Chem. 250: 4007.PubMedGoogle Scholar
  62. Orly, J., Sato, G., and Erickson, G. F., 1980, Serum suppresses the expression of hormonally induced functions in cultured granulosa cells, Cell 20: 817.PubMedCrossRefGoogle Scholar
  63. Osborne, C. K., Yockmowitz, M. G., Knight, W. A., and McGuire, W. L., 1980, The value of estrogen and progesterone receptors in the treatment of breast cancer, Cancer 46: 2884.PubMedCrossRefGoogle Scholar
  64. Paranjpe, M., Engel, L., Young, N., and Liotta, L. A., 1980, Activation of human breast carcinoma collagenase through plasminogen activator, Life Sci. 26: 1223.PubMedCrossRefGoogle Scholar
  65. Poole, A. R., Recklies, A. D., and Mort, J. S., 1980, Secretion of proteinases from human breast tumors: Excessive release from carcinomas of a thiol proteinase, in: Proteinases and Tumor Invasion ( A. J. Barrett, A. Baici and P. Strauli, eds.), pp. 81–95, Raven Press, New York.Google Scholar
  66. Quigley, J. P., Goldfarb, R. H., Scheiner, C., O’Donnell-Tormey, J., and Yeo, T. K., 1980, Plasminogen activator and the membrane of transformed cells, in: Tumor Cell Surfaces and Malignancy ( R. O. Hynes and C. F. Fox, eds.), pp. 773–796, Alan R. Liss, Inc., New York.Google Scholar
  67. Reiss, N., and Kaye, A. M., 1981, Identification of the major component of the estrogen-induced protein of rat uterus as the BB isoenzyme of creatine-kinase, J. Biol. Chem. 256: 5741.PubMedGoogle Scholar
  68. Shafie, S. M., 1980, Estrogen and the growth of breast cancer: New evidence suggests indirect action, Science 209: 701.PubMedCrossRefGoogle Scholar
  69. Shafie, S. M., and Liotta, L. A., 1980, Formation of metastasis by human breast carcinoma cells (MCF-7) in nude mice, Cancer Lett. 11: 81.PubMedCrossRefGoogle Scholar
  70. Sherman, M. R., Tuazon, F. B., and Miller, L. K., 1980, Estrogen receptor cleavage and plasminogen activation by enzymes in human breast tumor cytosol, Endocrinology 106: 1715.PubMedCrossRefGoogle Scholar
  71. Singhakowinta, A., Potter, H. G., Buroker, T. R., Samel, B., Brooks, S. C., and Vaitkervicius Google Scholar
  72. V. K., 1976, Estrogen receptor and natural course of breast cancer, Ann. Surg. 183: 84.CrossRefGoogle Scholar
  73. Sirbasku, D. A., 1980, Estromedins: Uterine-derived growth factors for estrogen-responsive tumor cells, in: Control Mechanisms in Animal Cells ( A. Shields, R. Levi-Montalcini, S. Iacobelli, and L. Jimenez de Asua, eds.), pp. 293–298, Raven Press, New York.Google Scholar
  74. Sirbasku, D. A., and Benson, R. H., 1980, Proposal of an indirect (estromedin) mechanism of estrogen-induced mammary tumor cell growth, in: Cell Biology of Breast Cancer ( C. McGrath, M. Brennan, and M. Rich, eds.), pp. 289–314, Academic Press, New York.Google Scholar
  75. Skipper, J. K., Eakle, S. D., and Hamilton, T. H., 1980, Modulation by estrogen of synthesis of specific uterine proteins, Cell 22: 69.PubMedCrossRefGoogle Scholar
  76. Stewart, J. F., King, R. J. B., Sexton, S. A., Millis, R. R., Rubens, R. D., and Haward, J. L., 1981, Oestrogen receptors, sites of metastatic disease and survival in recurrent breast cancer, Eur. J. Cancer 17: 449.PubMedGoogle Scholar
  77. Supowit, S. C., and Rosen, J. M., 1980, Gene expression in normal and neoplastic mammary tissue, Biochem. 19: 3432.Google Scholar
  78. Tata, J. R., 1979, Control by oestrogen of reversible gene expression: The vitellogenin model, J. Steroid Biochem. 11: 361.PubMedCrossRefGoogle Scholar
  79. Terenius, L., 1968, Selective retention of estrogen isomers in estrogen-dependent breast tumors of rats demonstrated by in vitro methods, Cancer Res. 28: 328.PubMedGoogle Scholar
  80. Toft, D., and Gorski, J., 1966, A receptor molecule for estrogens: Isolation from the rat uterus and preliminary characterization, Proc. Natl. Acad. Sci. U.S.A. 55: 1574.PubMedCrossRefGoogle Scholar
  81. Topper, Y. J., and Freeman, C. S., 1980, Multiple hormone interactions in the developmental biology of the mammary gland, Physiol. Rev. 60: 1049.Google Scholar
  82. Vignon, F. V., Terqui, M., Westley, B., Ducoq, D., and Rochefort, H., 1980, Effects of plasma estrogen sulfate in mammary cancer cells, Endocrinology 106: 1079.PubMedCrossRefGoogle Scholar
  83. Westley, B., and Rochefort, H., 1979, Estradiol induced proteins in the MCF-7 human breast cancer cell line, Biochem. Biophys. Res. Commun. 90: 410.CrossRefGoogle Scholar
  84. Westley, B., and Rochefort, H., 1980, A secreted glycoprotein induced by estrogen in human breast cancer cell lines, Cell 20: 353.PubMedCrossRefGoogle Scholar
  85. Yates, J., and King, R. J. B., 1981, Correlation of growth properties and morphology with hormone responsiveness of mammary tumor cells in culture, Cancer Res. 41: 258.Google Scholar
  86. Zava, D. T., and McGuire, W. L., 1978, Androgen action through the estrogen receptor in a human breast cancer cell line, Endocrinology 103: 624.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • David J. Adams
    • 1
  • Dean P. Edwards
    • 1
  • William L. McGuire
    • 1
  1. 1.Department of MedicineUniversity of Texas Health Science CenterSan AntonioUSA

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