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The Role of Estrogen Receptors in Breast Cancer Metastasis

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Abstract

It has long been appreciated that the estrogen receptor (ER) plays an important role in the biology of breast cancer. It is an accepted factor predicting favorable disease outcome and treatment response, and as such is generally considered to represent a “good” prognostic marker in breast cancer. In this review we present data suggesting that the ER may also play a pivotal role in the metastatic behavior of breast cancer, and present an argument that the up-regulation of ER and/or the selection of specific ER mutations are early events important for facilitating tumor progression. Thus, ER could serve dual roles in breast cancer, acting as a “bad” prognostic marker later in the disease process.

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REFERENCES

  1. W. C. Willett (1999). Epidemiology and assessing and managing risk. In J. R. Harris (ed.), Diseases of the Breast, 2nd edn., Lippincott Williams & Wilkins, Philadelphia, pp. 175-220.

    Google Scholar 

  2. S. Mosselman, J. Polman, and R. Dijkema (1996). ER β: Identification and characterization of a novel human estrogen receptor. FEBS Lett. 392:49-53.

    Google Scholar 

  3. L. Klein-Hitpass, G.U. Ryffel, E. Heitlinger, and A.C.B. Cato (1988). A13bp palindrome is a functional estrogen responsive element and interacts specifically with estrogen receptor. Nucleic Acids Res. 16:647-664.

    Google Scholar 

  4. P. Webb, G. N. Lopez, R. M. Uht, and P. J. Kushner (1995). Tamoxifen activation of the estrogen receptor/AP-1 pathway: Potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol. Endocrinol. 9:443-456.

    Google Scholar 

  5. P. Webb, P. Nguyen, C. Valentine, G. N. Lopez, G. R. Kwok, E. McInerney, B. S. Katzenellenbogen, E. Enmark, J. A. Gustafsson, S. Nilsson, and P. J. Kushner (1999). The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different requirements for receptor transactivation functions. Mol. Endocrinol. 13:1672-1685.

    Google Scholar 

  6. W. Porter, B. Saville, D. Hoivik, and S. Safe (1997). Functional synergy between the transcription factor Sp1 and the estrogen receptor. Mol. Endocrinol. 11:1569-1580.

    Google Scholar 

  7. S. L. Dana, P. A. Hoener, D. A. Wheeler, C. B. Lawrence, and D. P. McDonnel (1994). Novel estrogen response elements identified by genetic selection in yeast are differentially responsive to estrogen and antiestrogen in mammalian cells. Mol. Endocrinol. 8:1193-1207.

    Google Scholar 

  8. J.D. Norris, D. Fan, S. A. Kerner, and D. P. McDonnell (1997). Identification of a third autonomous activation domain within the human estrogen receptor. Mol. Endocrinol. 11:747-754.

    Google Scholar 

  9. V. Kumar, S. Green, G. Stack, M. Berry, J.-R. Jin, and P. Chambon (1987). Functional domains of the human estrogen receptor. Cell 51:941-951.

    Google Scholar 

  10. B. Pierrat, D. M. Heery, P. Chambon, and R. Losson (1994). A highly conserved region in the hormone-binding domain of the human estrogen receptor functions as an efficient transactivation domain in yeast. Gene 143:193-200.

    Google Scholar 

  11. S. M. Cowley and M. G. Parker (1999). A comparison of transcriptional activation by ERα and ERβ. J. Steroid Biochem. Mol. Biol. 69:165-175.

    Google Scholar 

  12. S. Ogawa, S. Inoue, T. Watanabe, H. Hiroi, A. Orimo, T. Hosoi, Y. Ouchi, and M. Muramatsu (1998). The complete primary structure of human estrogen receptor β (hERβ) and its heterodimerization with ER α in vivo and in vitro. Biochem. Biophys. Res. Commun. 243:122-126.

    Google Scholar 

  13. K. Pettersson, K. Grandien, G.G. Kuiper, and J.-A. Gustafsson (1997). Mouse estrogen receptor β forms estrogen response element-binding heterodimers with estrogen receptor α. Mol. Endocrinol. 11:1486-1496.

    Google Scholar 

  14. S. M. Cowley, S. Hoare, S. Mosselman, and M. G. Parker (1997). Estrogen receptors α and ß form heterodimers on DNA. J. Biol. Chem. 272:19858-19862.

    Google Scholar 

  15. J. Gustafsson (1999). Estrogen receptor beta-a new dimension in estrogen mechanism of action. J. Endocrinol. 163: 379-383.

    Google Scholar 

  16. J. H. Krege (1998). Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Natl. Acad. Sci. 95: 15677-15682.

    Google Scholar 

  17. E. R. Fisher, A. Palekar, H. Rockette, et al. (1978). Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol No. 4). V. Significance of axillary nodal micro-and macrometastasis. Cancer 42:2032-2038.

    Google Scholar 

  18. S. F. Honig (1996). Hormonal therapy and chemotherapy. In J. R. Harris, M. E. Lippman, M. Morrow, and S. Hellman (eds.), Diseases of the Breast, Lippincott-Raven, Philadelphia, pp. 669-734.

    Google Scholar 

  19. G. Bonadonna (1992). Evolving concepts in the systemic adjuvant treatment of breast cancer. Cancer Res. 52:2127-2137.

    Google Scholar 

  20. N. Macdonald and P. Steeg (1993). Molecular basis of tumor metastasis. Cancer Surv. 16:175.

    Google Scholar 

  21. P. Steeg (1996). Control of invasion and metastasis. In J. R. Harris, M. E. Lippman, M. Morrow, and S. Hellman (eds.), Diseases of the Breast, Lippencott-Raven, Philadelphia, pp. 284-292.

  22. P. A. Wingo, T. Tong, and S. Bolden (1995). Cancer statistics. CA Cancer J. Clin. 45:12.

    Google Scholar 

  23. L. Weiss, J. C. Holmes, and P. M. Ward (1983). Do metastases arise from preexisting sub-populations of cancer cells? Br. J. Cancer 47:81-89.

    Google Scholar 

  24. I. J. Fidler and I. R. Hart (1982). Biological diversity in metastatic neoplasms: Origins and implications. Science 217:893-895.

    Google Scholar 

  25. G. A. Niehans, T. P. SIngleton, D. Dykoski, and D. T. Kiang (1993). Stability of HER-2/neu expression over time and at multiple metastatic sites. J. Natl. Cancer Inst. 85:1230-1235.

    Google Scholar 

  26. B. A. Bonsing, P. Devilee, A. M. Cleton-Jansen, N. Kuipers-Dijkshoorn, G. J. Fleuren, and C. J. Cornelisse (1993). Evidence for limited molecular genetic heterogeneity as defined by allelotyping and clonal analysis in nine metastatic breast carcinomas. Cancer Res. 53:3804-3811.

    Google Scholar 

  27. L. C. Chen, W. Kuriso, B.M. Ljung, E. S. Goldman, D. Moore, and H. S. Smith (1992). Heterogeneity for allelic loss in human breast cancer. J. Natl. Cancer Inst. 84:505-510.

    Google Scholar 

  28. D. L. Page, W.D. Dupont, L.W. Rogers, and M. Landenberger (1982). Intraductal carcinoma of the breast: Follow-up after biopsy only. Cancer 49:751-758.

    Google Scholar 

  29. D. L. Page and W. D. Dupont (1993). Anatomic indicators (histological and cytologic) of increased breast cancer risk (review). Breast Cancer Res. Treat. 28:157-166.

    Google Scholar 

  30. P. O'Connell, V. Pekkel, S. A. W. Fuqua, C. K. Osborne, and D. C. Allred (1998). Analysis of loss of heterozygosity in 399 premalignant breast lesions at 15 genetic loci. J. Natl. Cancer Inst. 90:697-703.

    Google Scholar 

  31. D. M. Radford, K. L. Fair, N. J. Phillips, J. H. Ritter, T. Steinbrueck, and M. S. Holt (1995a). Allelotyping of ductal carcinoma in situ of the breast: Deletion of loci on 8p, 13q, 16q, 17p and 17q. Cancer Res. 55:3399-3405.

    Google Scholar 

  32. M. R. Stratton, N. Collins, S. R. Lakhani, and J. P. Sloane (1995). Loss of heterozygosity in ductal carcinoma in situ of the breast. J. Pathol. 175:195-201.

    Google Scholar 

  33. F. M. Waldman, S. DeVries, K. L. Chew, D. H. Moore, K. Kerlikowske, and B.-M. Ljung (2000). Chromosomal alterations in ductal carcinomas in situ and their in situ recurrences. J. Natl. Cancer Inst. 92:313-320.

    Google Scholar 

  34. D. L. Page, W. D. Dupont, L. W. Rogers, R. A. Jensen, and P. A. Schuyler (1995). Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer 76:1197.

    Google Scholar 

  35. D. C. Allred and S. K. Mohsin (2000). Biological features of human premalignant breast disease. In J. R. Harris, M. E. Lippman, M. Morrow, and C. K. Osborne (eds.), Diseases of the Breast, 2nd edn., LippincottWilliams and Wilkins, Philadelphia, pp. 355-366.

    Google Scholar 

  36. J. C. Allegra, M. E. Lippman, L. Green, A. Barlock, R. Simon, E. B. Thompson, K. K. Hugg, and W. Griffin (1979). Estrogen receptor values in patients with benign breast disease. Cancer 44:228-231.

    Google Scholar 

  37. D. Ricketts, L. Turnbull, G. Ryall, R. Bakhshi, N. S.B. Rawson, J.-C. Gazet, C. Nolan, and R.C. Coombes (1991). Estrogen and progesterone receptors in the normal female breast. Cancer Res. 51:1817-1822.

    Google Scholar 

  38. O. W. Peterson, P. E. Hoyer, and B. van Deurs (1986). Frequency and distribution of estrogen receptor-positive cells in normal, nonlactating human breast tissue. J. Natl. Cancer Inst. 77:343-349.

    Google Scholar 

  39. J. Russo, X. Ao, C. Grill, and I. H. Russo (1999). Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res. Treat. 53:217-227.

    Google Scholar 

  40. R. B. Clarke, A. Howell, C. S. Potten, and E. Anderson (1997). Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res. 57:4987-4991.

    Google Scholar 

  41. J. Russo, Y.-F. Hu, X. Yang, and I. H. Russo (2000). Developmental, cellular, and molecular basis of human breast cancer. J. Natl. Cancer Inst. Monogr. 27:17-37.

    Google Scholar 

  42. B. Zafrani, A. Leroyer, A. Fourquet, M. Laurent, D. Torphilme, P. Validire, et al. (1994). Mammographically detected ductal in situ carcinoma of the breast analyzed with a newclassification.Astudy of 127 cases: Correlation with estrogen and progesterone receptors, p53, and c-erbB-2 proteins, and proliferative activity. Sem. Diagn. Pathol. 11:208-214.

    Google Scholar 

  43. A. Chauchereau, J.-F. Savouret, and E. Milgrom (1992). Control of biosynthesis and post-transcriptional modification of the progesterone receptor. Biol. Reprod. 46:174-177.

    Google Scholar 

  44. L. Pallis, N. Wilking, B. Cedermark, L. E. Rutqvist, and L. Skoog (1992). Receptors for estrogen and progesterone in breast carcinoma in situ. Anticancer Res. 12:2113-2115.

    Google Scholar 

  45. A. J. Karayiannakis, E. A. Bastounis, E. B. Chatzigianni, G. G. Makri, D. Alexiou, and P. Karamanakos (1996). Immunohistochemical detection of oestrogen receptors in ductal carcinoma in situ of the breast. Eur. J. Surg. Oncol. 22:578-582.

    Google Scholar 

  46. S. A. W. Fuqua (1996). Estrogen and progesterone receptors and breast cancer. In J. R. Harris (ed.), Diseases of the Breast, Lippincott-Raven, Philadelphia, pp. 261-271.

    Google Scholar 

  47. S. A. W. Fuqua, C. Wiltschke, Q. X. Zhang, A. Borg, C. G. Castles, W. E. Friedrichs, T. Hopp, S. Hilsenbeck, S. Mohsin, P. O'Connell, and D. C. Allred (2000). A hypersensitive estrogen receptor-α mutation in premalignant breast lesions. Cancer Res. 60:4026-4029.

    Google Scholar 

  48. S. A. Khan, M. A. M. Rogers, and A. Tamsen (1994). Estrogen receptor expression of benign breast epithelium and its association with breast cancer. Cancer Res. 54:993-997.

    Google Scholar 

  49. S. A. Khan, M. A. Rogers, K. K. Khurana, M. M. Meguid, and P. J. Numann (1998). Estrogen receptor expression in benign breast epithelium and breast cancer risk. J. Natl. Cancer Inst. 90:37-42.

    Google Scholar 

  50. S. A. Khan, A. Sachedeva, S. Naim, M. M. Meguid, W. Marx, H. Simon, J. D. Halverson, and P. J. Numann (1999). The normal breast epithelium ofwomenwith breast cancer displays an aberrant response to estradiol. Cancer Epidemiol. Biomarkers Prev. 8:535-536.

    Google Scholar 

  51. E. Leygue, H. Dotzlaw, P.H. Watson, and L.C. Murphy (1998). Altered estrogen receptor α and β messenger RNA expression during human breast tumorigenesis. Cancer Res. 58:3197-3201.

    Google Scholar 

  52. K. Iwao, Y. Miyoshi, C. Egawa, N. Ikeda, and S. Noguchi (2000). Quantitative analysis of estrogen receptor β mRNA and its variants in human brest cancers. Int. J. Cancer 88:733-736.

    Google Scholar 

  53. P. Roger, M. E. Sahla, S. Makela, J. A. Gustafsson, P. Baldet, and H. Rochefort (2001). Decreased expression of estrogen receptor b protein in proliferative preinvasive mammary tumors. Cancer Res. 61:2537-2542.

    Google Scholar 

  54. I. Parra, G. M. Clark, R. Schiff, C. K. Osborne, D. C. Allred, and S. A. Fuqua (2001). Relationships between ERβ protein expression and other prognostic factors in breast cancer. Programs Abstr. 201.

  55. V. Speirs, A. T. Parkes, M. J. Kerin, D. S. Walton, P. J. Carleton, J. N. Fox, and S. L. Atkin (1999). Coexpression of estrogen receptor α and β: Poor prognostic factors in human breast cancer? Cancer Res. 59:525-528.

    Google Scholar 

  56. V. Speirs and M. J. Kerin (2000). Prognostic signifigance of oestrogen receptor beta in breast cancer. Br. J. Surg. 87:405-409.

    Google Scholar 

  57. J. M. Harvey (1999). Estrogen receptor status by immunohistochemistry is superior to the igand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J. Clin. Oncol. 17:1474-1481.

    Google Scholar 

  58. W. A. I. Knight, R. B. Livingston, E. J. Gregory, and W. L. McGuire (1977). Estrogen receptor is an independent prognostic factor for early recurrence in breast cancer. Cancer Res. 37:4669-4671.

    Google Scholar 

  59. G. M. Clark and W. L. McGuire (1988). Steroid receptors and other prognostic factors in primary breast cancer. Semin. Oncol. 15:20-25.

    Google Scholar 

  60. C. Carter, C. Allen, and D. Henson (1989). Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 63:181.

    Google Scholar 

  61. R.M. Elledge and S. A.W. Fuqua (2000). Estrogen and progesterone receptors. In J. R. Harris, M. E. Lippman, M. Morrow, and C. K. Osborne (eds.), Diseases of the Breast, Vol. 2, Lippincott,Williams & Wilkins, Philadelphia,PA, pp. 471-488.

    Google Scholar 

  62. W. R. Bezwoda, J. D. Esser, R. Dansey, I. Kessel, T. M. M. Rad, and M. Lange (1991). The value of estrogen and progesterone receptor determinations in advance breast cancer. Cancer 68:867-872.

    Google Scholar 

  63. C. Rose and H. T. Mouridsen (1984). Treatment of advanced breast cancer with tamoxifen. Recent Results Cancer Res. 91:230.

    Google Scholar 

  64. D. G. Bratherton, C. H. Brown, R. Buchanan, et al. (1984). A comparison of two doses of tamoxifen (Nolvadex) in postmenopausal women with advanced breast cancer: 10MG BD versus 20 MG BD. Br. J. Cancer 50:199.

    Google Scholar 

  65. Early Breast Cancer Trialists' Collaborative Group (1998). Tamoxifen for early breast cancer: An overview of the randomised trials. Lancet 351:1451-1467.

    Google Scholar 

  66. Early Breast Cancer Trialists' Collaborative Group (1992). Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomized trials involving 31000 recurrences and 24000 deaths among 75000 women. Lancet 339:1-15, 71-85.

    Google Scholar 

  67. Early Breast Cancer Trialists Collaborative Group (1988). Effects of adjuvant tamoxifen and of cytotoxic therapy onmortality in early breast cancer: An overview of 61 randomized trials among 28,896 women. N. Engl. J. Medicine 319:1681-1692.

    Google Scholar 

  68. C. Hermon and V. Beral (1996). Breast cancer mortality rates are levelling off or beginning to decline in many western countries: Analysis of time trends, age-cohort and age-period models of breast cancer mortality in 20 countries. Br. J. Cancer 73:955.

    Google Scholar 

  69. D. F. Hull, G. M. Clark, C. K. Osborne, G. C. Chamness, W. A. I. Knight, and W. L. McGuire (1983). Multiple estrogen receptor assays in human breast cancer. Cancer Res. 43:413-416.

    Google Scholar 

  70. J. Robertson (1996). Oestrogen receptor: A stable phenotype in breast cancer. Br. J. Cancer 73:5-12.

    Google Scholar 

  71. L. Nedergaard, T. Haerslev, and G. K. Jacobsen (1995). Immunohistochemical study of estrogen receptors in primary breast carcinomas and their lymph node metastases including comparison of two monoclonal antibodies. APMIS 103:20-24.

    Google Scholar 

  72. 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. 51:105-109.

    Google Scholar 

  73. S. A. W. Fuqua, S. D. Fitzgerald, D. C. Allred, R. M. Elledge, Z. Nawaz, D. P. McDonnell, B. W. O'Malley, G. L. Greene, and W. L. McGuire (1992). Inhibition of estrogen receptor action by a naturally occurring variant inhumanbreast tumors. Cancer Res. 52:483-486.

    Google Scholar 

  74. T. A. Hopp and S. A. Fuqua (1998). Estrogen receptor variants. J. Mamm. Gland Biol. Neoplasia 3:73-83.

    Google Scholar 

  75. L. C. Murphy, H. Dotzlaw, E. Leygue, A. Coutts, and P. Watson (1997). The pathophysiological role of estrogen receptor variants in human breast cancer. J. Steroid Biochem. Mol. Biol. 65:1-6.

    Google Scholar 

  76. E. Leygue, R. E. Hall, H. Dotzlaw, P. H. Watson, and L. C. Murphy (1999). Oestrogen receptor α variant mRNA expression in primary human breast tumours and matched lymph node metastases. Br. J. Cancer 79:978-983.

    Google Scholar 

  77. R. Reddel, I. Alexander, M. Koga, J. Shine, and R. Sutherland (1988). Genetic instability and the development of steroid hormone insensitivity in cultured T 47D human breast cancer cells. Cancer Res. 48:4340-4347.

    Google Scholar 

  78. M. L. Graham, N. L. Krett, L. A. Miller, K. K. Leslie, D. F. Gordon, W. M. Wood, L. L. Wei, and K. B. Horwitz (1990). T47Dco cells, genetically unstable and containing estrogen receptor mutations, are a model for the progression of breast cancers to hormone resistance. Cancer Res. 50:6208-6217.

    Google Scholar 

  79. M. L. Graham, J. A. Smith, P. B. Jewett, and K. B. Horwitz (1992). Heterogeneity of progesterone receptor content and remodeling by tamoxifen characterize subpopulations of cultured human breast cancer cells: Analysis by quantitative dual parameter flow cytometry. Cancer Res. 52:593-602.

    Google Scholar 

  80. M. M. Montano and B. S. Katzenellenbogen (1997). The quinone reductase gene: A unique estrogen receptorregulated gene that is activated by antiestrogens. Proc. Natl. Acad. Sci. U.S.A. 94:2581-2586.

    Google Scholar 

  81. B. S. Katzenellenbogen, K. L. Kendra, M. J. Norman, and Y. Berthois (1987). Proliferation, hormone responsiveness and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. Cancer Res. 47:4355-4360.

    Google Scholar 

  82. J. J. Pink, M. M. Bilimoria, J. Assikis, and V. C. Jordan (1996). Irreversible loss of the estrogen receptor in T47D breast cancer cells following prolonged oestrogen deprivation. Br. J. Cancer 74:1227-1236.

    Google Scholar 

  83. C. S. Murphy, J. J. Pink, and V. C. Jordan (1990). Characterization of a receptor-negative, hormone-nonresponsive clone derived from a T47D human breast cancer cell line kept under estrogen-free conditions. Cancer Res. 50:7285-7292.

    Google Scholar 

  84. D. Miller, D. El-Ashry, A. Cheville, Y. Liu, S. McLeskey, and F. Kern (1994). Emergence of MCF7 cells overexpressing a transfected epidermal growth factor receptor (EGFR) under estrogen-depleted conditions: Evidence for a role of EGFR in breast cancer growth and progression. Cell Growth Differ. 5:1263-1274.

    Google Scholar 

  85. C.C. Benz, G. K. Scott, J.C. Sarup, R.M. Johnson, D. Tripathy, E. Coronado, H. M. Shepard, and C. K. Osborne (1993). Estrogen-dependant, tamoxifen-resistant tumorigenic growth ofMCF-7cells transfected with HER2/neu. Breast Cancer Res. Treat. 24:85-95.

    Google Scholar 

  86. S.-Y. Jiang, D. M. Wolf, J. M. Yingling, C. Chang, and V. C. Jordan (1992). An estrogen receptor positve MCF-7 clone that is resistant to antiestrogens and estradiol. Mol. Cell. Endocrinol. 90:77-86.

    Google Scholar 

  87. D. El-Ashry, D. Miller, S. Kharbanda, M. Lippman, and F. Kern (1997). Constitutive Raf-1 kinase activity in breast cancer cells induces both estrogen-independent growth and apoptosis. Oncogene 15:423-435.

    Google Scholar 

  88. S. Wise, L. Smith, D. Hendricks, A. Sabichi, M. Bober, P. Brown, and M. Birrer (1997). Over-expression of the cJun oncoprotein in the human breast cancer cell line MCF-7 results in tamoxifen resistance and increased invasiveness. Proc. Am. Assoc. Cancer Res. 38:173.

    Google Scholar 

  89. S. J. Nass and R. B. Dickson (1997). Defining a role for c-myc in breast tumorigenesis. Breast Cancer Res. Treat. 44:1.

    Google Scholar 

  90. M. Alkahalf and L. C. Murphy (1992). Regulation of c-jun and jun B by progestins in T47D human breast cancer cells. Mol. Endocrinol. 6:1625.

    Google Scholar 

  91. J. K. Ruohola, E. M. Valve, M. J. Karkkainen, V. Joukov, K. Alitalo, and P. L. Harkonen (1999). Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells. Mol. Cell. Endocrinol. 149:29-40.

    Google Scholar 

  92. S. M. Hyder, Z. Nawaz, C. Chiappetta, and G. M. Stancel (2000). Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Cancer Res. 60:3183-3190.

    Google Scholar 

  93. S. M. Hyder, J. C. Huang, Z. Nawaz, H. Boettger-Tong, S. Makela, C. Chiappetta, and G. M. Stancel (2000). Regulation of vascular endothelial growth factor expression by estrogens and progestins. Environ. Health Perspect. 108:785-790.

    Google Scholar 

  94. M. S. Pepper, N. Ferrara, L. Orci, and R. Montesano (1992). Potent synergism between vascular endothelial growth factor and basic fiborblast growth factor in the induction of angiogenesis in vitro. Biochem. Biophys. Res. Commun. 189:824.

    Google Scholar 

  95. M. Friedlander, P. C. Brooks, R.W. Shaffer, et al. (1995). Defi-nition of two angiogenic pathways by distinct alpha v integrins. Science 270:1500.

    Google Scholar 

  96. P. H. Hand, A. Thor, J. Schlom, C.N. Rao, and L. Liotta (1985). Expression of laminin receptor in normal and carcinomatous human tissues as defined by a monoclonal antibody. Cancer Res. 45:2713.

    Google Scholar 

  97. V. Castronovo, G. Taraboletti, L. A. Liotta, et al. (1989). Modulation of laminin receptor expression by estrogen and progestin in human breast cancer cell lines. J. Natl. Cancer Inst. 81:781.

    Google Scholar 

  98. H. Rochefort (1995). Oestrogen-and anti-oestrogenregulated genes in human breast cancer. Ciba Foundation Symp. 191:254-268.

    Google Scholar 

  99. M. Garcia, N. Platet, E. Liaudet, V. Laurent, D. Deroeg, J. P. Brouillet, and H. Rochefort (1996). Biological and clinical significance of cathepsin D in breast cancer metastasis. Stem Cells 14:642.

    Google Scholar 

  100. F. A. van den Brule, J. Engel, W.G. Stetler-Stevenson, F. T. Liu, M. E. Sobel, and V. Castronovo (1992). Genes involved in tumor invasion and metastasis are differentially modulated by estradiol and progestin in human breast-cancer cells. Int. J. Cancer 52:653-657.

    Google Scholar 

  101. A. V. Lee, C. N. Weng, J. G. Jackson, and D. Yee (1997). Activation of estrogen receptor-mediated gene transcription by IGF-I in human breast cancer cells. J. Endocrinol. 152:39-47.

    Google Scholar 

  102. C. A. Molloy, F. E. May, and B. R. Westley (2000). Insulin receptor substrate-1 expression is regulated by estrogen in the MCF-7 human breast cancer cell line. J. Biol. Chem. 275:12565-12571.

    Google Scholar 

  103. M. Jorgensen, B. Vendelbo, N. E. Skakkebaek, and H. Leffers (2000). Assaying estrogenicity by quantitating the expression levels of endogenous estrogen-regulated genes. Environ. Health Perspect. 108:403-412.

    Google Scholar 

  104. P. G. Koenders, L. V. Beex, R. Langens, P. W. Kloppenborg, A. G. Smals, and T. J. Benraad (1991). Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis. The Breast Cancer Study Group. Breast Cancer Res. Treat. 18:27-32.

    Google Scholar 

  105. J. E. Gervasoni, C. Taneja, M. A. Chung, and B. Cady (2000). Axillary dissection in the context of the biology of lymph node metastases. Am. J. Surg. 180:278-283.

    Google Scholar 

  106. S. Paget (1989). The distribution of secondary growths in cancer of the breast. Lancet I:571-573.

    Google Scholar 

  107. R. E. Coleman and R. D. Rubens (1987). The clinical course of bone metastases from breast cancer. Br. J. Cancer 55:61-66.

    Google Scholar 

  108. T. Yoneda (2000). Cellular and molecular basis of preferential metastasis of breast cancer to bone. J. Orthop. Sci. 5:75-81.

    Google Scholar 

  109. J. T. Moore, D. D. McKee, K. Slentz-Kesler, L. B. Moore, S. A. Jones, E.L. Horne, J.-L. Su, S. A. Kliewer, J.M. Lehmann, and T. M. Willson (1998). Cloning and characterization of human estrogen receptor β isoforms. Biochem. Biophys. Res. Commun. 247:75-78.

    Google Scholar 

  110. S. A. Fuqua, R. Schiff, I. Parra, W. E. Friedrichs, J. L. Su, D.D. McKee, K. Slentz-Kesler, L.B. Moore, T.M. Willson, and J. T. Moore (1999). Expression of wild-type estrogen receptor β and variant isoforms in human breast cancer. Cancer Res. 59:5425-5428.

    Google Scholar 

  111. P. S. Karnik, S. Kulkarni, X.-P. Liu, G. T. Budd, and R. M. Bukowski (1994). Estrogen receptor mutations in tamoxifen-resistant breast cancer. Cancer Res. 54:349-353.

    Google Scholar 

  112. Q. X. Zhang, A. Borg, D. M. Wolf, S. Oesterreich, and S. A. Fuqua (1997). An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res. 57:1244-1249.

    Google Scholar 

  113. K. E. Weis, K. Ekena, J. A. Thomas, G. Lazennec, and B. S. Katzenellenbogen (1996). Constitutively active human estrogen receptors containing amino acid substitutions for tyrosine 537 in the receptor protein. Mol. Endocrinol. 10:1388-1398.

    Google Scholar 

  114. A. Tremblay, G. B. Tremblay, F. Labrie, and V. Giguere (1999). Ligand-independent recruitment of SRC-1 to estrogen receptor β through phosphorylation of activation function AF-1. Mol. Cell 3:513-519.

    Google Scholar 

  115. S. F. Arnold, D. P. Vorojeikina, and A.C. Notides (1995). Phosphorylation of tyrosine 537 on the human estrogen receptor is required for binding to an estrogen response element. J. Biol. Chem. 270:30205-30212.

    Google Scholar 

  116. A. Migliaccio, D. Piccolo, G. Castoria, M. Di Domenico, A. Bilancio, M. Lombardi, W. Gong, M. Beato, and F. Auricchio (1998). Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor. EMBO J. 17:2008-2018.

    Google Scholar 

  117. S. A.W. Fuqua, T. Hopp, M. Van, C. K. Osborne, P. O'Connell, S. Hilsenbeck, and D. C. Allred (2001). An estrogen receptor α mutation that predicts metastatic breast cancer clinical behavior. In 9th SPORE Investigators' Workshop, p. 174.

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Fuqua, S.A.W. The Role of Estrogen Receptors in Breast Cancer Metastasis. J Mammary Gland Biol Neoplasia 6, 407–417 (2001). https://doi.org/10.1023/A:1014782813943

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