The molecular mechanisms underlying the pharmacological actions of ER modulators: Implications for new drug discovery in breast cancer

Current Opinion in Pharmacology

Volumn 10, Issue 6, 2010, Pages 620-628

  McDonnell, Donald P ^a   Wardell, Suzanne E ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1,2 DIPHENYL 1 BUTENYL)CINNAMIC ACID; AROMATASE INHIBITOR; BAZEDOXIFENE; DPC 974; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTRADIOL; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FULVESTRANT; GROWTH FACTOR RECEPTOR; LAPATINIB; LASOFOXIFENE; PROTEIN HOXB13; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; STEROID RECEPTOR COACTIVATOR 1; STEROID RECEPTOR COACTIVATOR 3; TAMOXIFEN; TRANSCRIPTION FACTOR; TRASTUZUMAB; UNCLASSIFIED DRUG;

BINDING AFFINITY; BREAST CANCER; BREAST TUMOR; CANCER INHIBITION; CLINICAL TRIAL; DNA BINDING; DNA CONFORMATION; DRUG CONFORMATION; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG RESEARCH; DRUG SENSITIVITY; GENE TARGETING; HUMAN; LIGAND BINDING; MITOGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; TRANSACTIVATION; TRANSCRIPTION REGULATION;

ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CLINICAL TRIALS AS TOPIC; DRUG DISCOVERY; DRUG PARTIAL AGONISM; ESTROGEN RECEPTOR MODULATORS; FEMALE; HUMANS; LIGANDS; MOLECULAR CONFORMATION; MOLECULAR TARGETED THERAPY; NUCLEAR RECEPTOR COACTIVATORS; RECEPTORS, ESTROGEN; SELECTIVE ESTROGEN RECEPTOR MODULATORS; SIGNAL TRANSDUCTION; TRANSCRIPTIONAL ACTIVATION;

EID: 78149501152     PISSN: 14714892     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coph.2010.09.007     Document Type: Review

References (75)

1. Clemens J.A., Bennet D.R., Black L.J., Jones C.D. Effects of a new anti-estrogen, keoxifene (LY156758), on growth of carcinogen-induced mammary tumors and on LH and prolactin secretion. Life Sci 1983, 32:2869-2875.
2. Jordan V.C., Collins M.M., Rowsby L., Prestwich G. A mono-hydroxylated metabolite of tamoxifen with potent antioestrogen activity. J Endocrinol 1977, 75:305-316.
3. Harper M.J.K., Walpole A.L. Contrasting endocrine activities of cis and trans isomers in a series of substituted triphenylethylenes. Nature 1966, 212:87-89.
4. Turner C.H., Sato M., Bryant H.U. Raloxifene preserves bone strength and bone mass in ovariectomized rats. Endocrinology 1994, 135:2001-2005.
5. Turner R.T., Wakley G.K., Hannon K.S., Bell N.H. Tamoxifen prevents the skeletal effects of ovarian hormone deficiency in rats. J Bone Miner Res 1987, 2:449-456.
6. Gottardis M.M., Robinson S.P., Satyaswaroop P.G., Jordan V.C. Contrasting actions of tamoxifen on endometrial and breast tumor growth in the athymic mouse. Cancer Res 1988, 48:812-815.
7. McDonnell D.P., Clemm D.L., Hermann T., Goldman M.E., Pike J.W. Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol 1995, 9:659-668.
8. Gottardis M.M., Jordan V.C. Development of tamoxifen-stimulated growth of MCF-7 tumors in athymic mice after long-term antiestrogen administration. Cancer Res 1988, 48:5183-5187.
9. Canney P.A., Griffiths T., Latief T.N., Priestman T.J. Clinical significance of tamoxifen withdrawal response. Lancet 1987, 1:36.
10. Love R.R., Mazess R.B., Barden H.S., Epstein S., Newcomb P.A., Jordan V.C., Carbone P.P., DeMets D.L. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. New Engl J Med 1992, 326:852-856.
11. Cummings S.R., Eckert S., Krueger K.A., Grady D., Powles T.J., Cauley J.A., Norton L., Nickelsen T., Bjarnason N.H., Morrow M., et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. JAMA 1999, 281:2189-2197.
12. Safe S., Kim K. Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways. J Mol Endocrinol 2008, 41:263-275.
13. Stender J.D., Kim K., Charn T.H., Komm B., Chang K.C.N., Kraus W.L., Benner C., Glass C.K., Katzenellenbogen B.S. Genome-wide analysis of estrogen receptor alpha DNA binding and tethering mechanisms identifies Runx1 as a novel tethering factor in receptor-mediated transcriptional activation. Mol Cell Biol 2010, 30:3943-3955.
14. Hall J.M., McDonnell D.P. Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting. Mol Interv 2005, 5:343-357.
15. Kuiper G.G.J.M., Carlsson B., Grandien K., Enmark E., Häggblad J., Nilsson S., Gustafsson J.-A. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors a and b. Endocrinology 1997, 138:863-870.
16. Hall J.M., McDonnell D.P. The estrogen receptor b-isoform (ERb) of the human estrogen receptor modulates ERa transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 1999, 140:5566-5578.
17. Vanacker J.-M., Pettersson D., Gustafsson J.-Å., Laudet v. Transcriptional targets shared by estrogen receptor-related receptors (ERRs) and estrogen receptor (ER) a, but not by ERb. EMBO J 1999, 18:4270-4279.
18. Paech K., Webb P., Kuiper G.G.J.M., Nilsson S., Gustafsson J.-A., Kushner P.J., Scanlan T.S. Differential ligand activation of estrogen receptors ERa and ERb at AP1 sites. Science 1997, 277:1508-1510.
19. Barkhem T., Carlsson B., Milsson Y., Enmark E., Gustafsson J.-A., Nilsson S. Differential response of estrogen receptor a and estrogen receptor b to partial estrogen agonists/antagonists. Mol Pharmacol 1998, 54:105-112.
20. Peekhaus N.T., Chang T., Hayes E.C., Wilkinson H.A., Mitra S.W., Schaeffer J.M., Rohrer S.P. Distinct effects of the antiestrogen Faslodex on the stability of estrogen receptors-a and -b in the breast cancer cell line MCF-7. J Mol Endocrinol 2004, 32:987-995.
21. Hou Y.F., Yuan S.T., Li H.C., Wu J., Lu J.S., Liu G., Lu L.J., Shen Z.Z., Ding J., Shao Z.M. ERb exerts multiple stimulative effects on human breast carcinoma cells. Oncogene 2004, 23:5799-5806.
22. 2 cell cycle arrest. Cancer Res 2004, 64:423-428.
23. Gee A.C., Carlson K.E., Martini P.G.V., Katzenellenbogen B.S., Katzenellenbogen J.A. Coactivator peptides have a differential stabilizing effect on the binding of estrogens and antiestrogens with the estrogen receptor. Mol Endocrinol 1999, 13:1912-1923.
24. Hall J.M., McDonnell D.P., Korach K.S. Allosteric regulation of estrogen receptor structure, function, and coactivator recruitment by different estrogen response elements. Mol Endocrinol 2002, 16:469-486.
25. Dana S.L., Hoener P.A., Wheeler D.L., Lawrence C.L., McDonnell D.P. Novel estrogen response elements identified by genetic selection in yeast are differentially responsive to estrogens and antiestrogens in mammalian cells. Mol Endocrinol 1994, 8:1193-1207.
26. Clemm D.L., Macy B.L., Santiso-Mere D., McDonnell D.P. Definition of the critical cellular components which distinguish between hormone and antihormone activated progesterone receptor. J Steroid Biochem Mol Biol 1995, 53:487-495.
27. Crabtree J.S., Peano B.J., Zhang X., Komm B.S., Winneker R.C., Harris H.A. Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland. Mol Cell Endocrinol 2008, 287:40-46.
28. Strom A., Hartman J., Foster J.S., Kietz S., Wimalasena J., Gustafsson J.-Å. Estrogen receptor b inhibits 17b-estradiol-stimulated proliferation of the breast cancer cell line T47D. Proc Natl Acad Sci USA 2004, 101:1566-1571.
29. Fisher B., Dignam J., Bryant J., Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst 2001, 93:684-690.
30. Smith C.L., Nawaz Z., O'Malley B.W. Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen. Mol Endocrinol 1997, 11:657-666.
31. Wijayaratne A.L., Nagel S.C., Paige L.A., Christensen D.J., Norris J.D., Fowlkes D.M., McDonnell D.P. Comparative analyses of the mechanistic differences among antiestrogens. Endocrinology 1999, 140:5828-5840.
32. Anzick S.L., Kononen J., Walker R.L., Azorsa D.O., Tanner M.M., Guan X.-Y., Sauter G., Kallioniemi O.-P., Trent J.M., Meltzer P.S. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 1997, 277:965-968.
33. Osborne C.K., Bardou V., Hopp T.A., Chamness G.C., Hilsenbeck S.G., Fuqua S.A.W., Wong J., Allred D.C., Clark G.M., Schiff R. Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J Natl Cancer Inst 2003, 95:353-361.
34. Redmond A.M., Bane F.T., Stafford A.T., McIlroy M., Dillon M.F., Crotty T.B., Hill A.D., Young L.S. Coassociation of estrogen receptor and p160 proteins predicts resistance to endocrine treatment: SRC-1 is an independent predictor of breast cancer recurrence. Clin Cancer Res 2009, 15:2098-2106.
35. Shou J., Mssarweh S., Osborne C.K., Wakeling A.E., Schiff R. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst 2004, 96:926-935.
36. Kurokawa H., Lenferink A.E.G., Simpson J.F., Pisacane P.I., Sliwkowski M.X., Forbes J.T., Arteaga C.L. Inhibition of HERs/neu (erbB-2) and mitogen-activated protein kinases enhances tamoxifen action against HER2-overexpressing, tamoxifen-resistant breast cancer cells. Cancer Res 2000, 60:5887-5894.
37. Yue W., Wang J.-P., Conaway M., Masamura S., Li Y., Santen R.J. Activation of the MAPK pathway enhances sensitivity of MCF-7 breast cancer cells to the mitogenic effect of estradiol. Endocrinology 2002, 143:3221-3229.
38. Fujimoto N., Katzenellenbogen B.S. Alteration in the agonist/antagonist balance of antiestrogens by activation of protein kinase A signaling pathways in breast cancer cells: antiestrogen selectivity and promoter dependence. Mol Endocrinol 1994, 8:296-304.
39. Gee J.M., Robertson J.F., Gutteridge E., Ellis I.O., Pinder S.E., Rubini M., Nicholson R.I. Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signaling and oestrogen receptor activity in clinical breast cancer. Endocr Relat Cancer 2005, 12:S99-S111.
40. Carascossa S., Dudek P., Cenni B., Briand P.-A., Picard D. CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor alpha by cAMP. Genes Dev 2010, 24:708-719.
41. Mora JFd, Brown M. AIB1 is a conduit for kinase-mediated growth factor signaling to the estrogen receptor. Mol Cell Biol 2000, 20:5041-5047.
42. Xia W., Bacus S., Hegde P., Husain I., Strum J., Liu L., Paulazzo G., Lyass L., Trusk P., Hill J., et al. A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. Proc Natl Acad Sci USA 2006, 103:7795-7800.
43. Hurtado A., Holmes K.A., Geistlinger T.R., Hutcheson I.R., Nicholson R.I., Brown M., Jiang J., Howat W.J., Ali S., Carroll J.S. Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature 2008, 456:663-667.
44. Moi L.L.H., Flageng M.H., Gandini S., Guerrieri-Gonzaga A., Bonanni B., Lazzeroni M., Gjerde J., Lien E.A., Censi A.D., Mellgren G. Effect of low-dose tamoxifen on steroid receptor coactivator 3/amplified in breast cancer 1 in normal and malignant human breast tissue. Clin Cancer Res 2010, 16:2176-2186.
45. Goetz M.P., Suman V.J., Ingle J.N., Nibbe A.M., Visscher D.W., Reynolds C.A., Lingle W.L., Erlander M., Ma X.-J., Sgroi D.C., et al. A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen. Clin Cancer Res 2006, 12:2080-2087.
46. Ma X.-J., Wang Z., Ryan P.D., Isakoff S.J., Barmettler A., Fuller A., Muir B., Mohapatra g, Salunga R., Tuggle J.T., et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell 2004, 5:607-616.
47. Ma X.-J., Hilsenbeck S.G., Wang W., Ding L., Sgroi D.C., Bender R.A., Osborne C.K., Allred D.C., Erlander M.G. The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol 2006, 24:4611-4619.
48. Norris J.D., Fan D., Sherk A., McDonnell D.P. A negative coregulator for the human ER. Mol Endocrinol 2002, 16:459-468.
49. Yeo G.W., Coufal N.G., Liang T.Y., Peng G.E., Fu X.-D., Gage F.H. An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells. Nat Struct Mol Biol 2009, 16:130-137.
50. Moore T.W., Mayne C.G., Katzenellenbogen J.A. Minireview: not picking pockets: Nuclear Receptor Alternate-site Modulators (NRAMs). Mol Endocrinol 2010, 24:683-695.
51. Parent A.A., Gunther J.R., Katzenellenbogen J.A. Blocking estrogen signaling after the hormone: pyrimidine-core inhibitors of estrogen receptor-coactivator binding. J Med Chem 2008, 51:6512-6530.
52. Buzdar A.U., Marcus C., Holmes F., Hug V., Hortobachi G. Phase II evaluation of LY156758 in metastatic breast cancer. Oncology 1988, 45:144-145.
53. Norris J.D., Paige L.A., Christensen D.J., Chang C.-Y., Huacani M.R., Fan D., Hamilton P.T., Fowlkes D.M., McDonnell D.P. Peptide antagonists of the human estrogen receptor. Science 1999, 285:744-746.
54. Brzozowski A.M., Pike A.C., Dauter Z., Hubbard R.E., Bonn T., Engstrom O., Ohman L., Greene G.L., Gustafsson J.A., Carlquist M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997, 389:753-758.
55. Shiau A.K., Barstad D., Loria P.M., Cheng L., Kushner P.J., Agard D.A., Greene G.L. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 1998, 95:927-937.
56. Vogel V.G. The NSABP Study of Tamoxifen and Raloxifene (STAR) trial. Expert Rev Anticancer Ther 2009, 9:51-60.
57. Vogel V.G., Costantino J.P., Wickerham D.L., Cronin W.M., Cecchini R.S., Atkins J.N., Bevers T.B., Fehrenbacher L., Pajon E.R., Wade J.L., et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes. JAMA 2007, 295:2727-2741.
58. Vogel V.G., Costantino J.P., Wickerham D.L., Cronin W.M., Cecchini R.S., Atkins J.N., Bevers T.B., Fehrenbacher L., Pajon E.R., Wade J.L., et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 trial: preventing breast cancer. Cancer Prev Res (Phila Pa) 2010, 3:696-706.
59. Wu Y.-L., Yang X., Ren Z., McDonnell D.P., Norris J.D., Willson T.M., Greene G.L. Structural basis for an unexpected mode of SERM-mediated ER antagonism. Mol Cell 2005, 18:413-424.
60. Connor C.E., Norris J.D., Broadwater G., Willson T.M., Gottardis M.M., Dewhirst M.W., McDonnell D.P. Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor. Cancer Res 2001, 61:2917-2922.
61. Peethambaram P.P., Ingle J.N., Suman V.J., Hartann L.C., Loprinzi C.L. Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis. Breast Cancer Res Treat 1999, 54:117-122.
62. Osborne C.K., Coronado-Heinson E.B., Hilsenbeck S.G., McCue B.L., Wakeling A.E., McClelland R.A., Nicholson R.I. Comparison of the effects of a pure steroidal antiestrogen with those of tamoxifen in a model of human breast cancer. J Natl Cancer Inst 1995, 87:746-750.
63. Howell A., DeFriend D., Robertson J., Blamey R., Walton P. Response to a specific antiestrogen (ICI182,780) in tamoxifen-resistant breast cancer. Lancet 1995, 345:29-30.
64. Creighton C.J., Massarweh S., Huang S., Tsimelzon A., Hilsenbeck S.G., Osborne C.K., Shou J., Malomi L., Schiff R. Development of resistance to targeted therapies transforms the clinically associated molecular profile subtype of breast tumor xenografts. Cancer Res 2008, 68:7493-7501.
65. Young O.E., Renshaw L., Macaskill E.J., White S., Faratian D., Thomas J.S.J., Dixon J.M. Effects of fulvestrant 750mg in premenopausal women with oestrogen-receptor-positive primary breast cancer. Eur J Cancer 2008, 44:391-399.
66. Robertson J.F.R. Fulvestrant (Faslodex)-how to make a good drug better. Oncologist 2007, 12:774-784.
67. Gutteridge E., Robertson J.F.R., Cheung K.L. Effects of fulvestrant on estrogen receptor levels during long-term treatment of patients with advanced breast cancer-final results. Breast Cancer Res Treat 2004, 88(Suppl. 1):S177.
68. Robertson J.F., Llombart-Cussac A., Rolski J., Feltl D., Dewar J., Macpherson E., Lindemann J., Ellis M.J. Activity of fulvestrant 500mg versus anastrozole 1mg as first-line treatment for advanced breast cancer: results from the FIRST study. J Clin Oncol 2009, 27:4530-4535.
69. Leo A.D., Jerusalem G., Petruzelka L., Torres R., Bondarenko I., Khasanov R., Verhoeven D., Pedrini J., Lichinitser M., Pendergrass K., et al. CONFIRM: a Phase III, randomized, parallel-group trial comparing fulvestrant 250mg vs fulvestrant 500mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. Cancer Res 2009, 69(24 Suppl.). Abstract nr 25.
70. Wittmann B.M., Sherk A., McDonnell D.P. Definition of functionally important mechanistic differences among selective estrogen receptor down-regulators. Cancer Res 2007, 67:9549-9560.
71. Kieser K.J., Kim D.W., Carlson D.E., Katzenellenbogen B.S., Katzenellenbogen J.A. Characterization of the pharmacophore properties of novel Selective Estrogen Receptor Downregulators (SERDs). J Med Chem 2010, 53:3320-3329.
72. Santen R., Jeng M.-H., Wang J.-P., Song R., Masamura S., McPherson R., Santner S., Yue W., Shim W.-S. Adaptive hypersensitivity to estradiol: potential mechanism for secondary hormonal responses in breast cancer patients. J Steroid Biochem Mol Biol 2001, 79:115-125.
73. DuSell C.D., Umetani M., Shaul P.W., Mangelsdorf D.J., McDonnell D.P. 27-hydroxycholesterol is an endogenous selective estrogen receptor modulator. Mol Endocrinol 2008, 22:65-77.
74. Sikora M.J., Cordero K.E., Larios J.M., Johnson M.D., Lippman M.E., Rae J.M. The androgen metabolite 5 alpha-androstane-3 beta, 17 beta-diol (3 alpha Adiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance. Breast Cancer Res Treat 2009, 115:289-296.
75. Robertson J.F., Steger G.G., Neven P., Barni S., Gieseking F., Nole F., Pritchard K.I., O'Malley F.P., Simon S.D., Kaufman B. Activity of fulvestrant in HER2-overexpressing advanced breast cancer. Ann Oncol 2010, 21:1246-1253.