The ER/AP1 Pathway: A Window on the Cell-Specific Estrogen-like Effects of Antiestrogens

  • P. Webb
  • M.-R. Keneally
  • J. Shinsako
  • R. Uht
  • C. Anderson
  • K. Paech
  • T. S. Scanlan
  • P. J. Kushner
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 24)

Abstract

We study an unusual pathway of estrogen receptor (ER) action, in which ER indirectly alters the transactivation capacity of the jun/fos complex (AP1 proteins), rather than stimulating gene expression by directly binding DNA. Here, we review the rationale for studying this pathway and the reasons for thinking that elucidation of ER/AP1 interactions will help us design the next generation of antiestrogens and hormone replacement therapies.

Keywords

Estrogen Serine Dexamethasone Tamoxifen Glucocorticoid 

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References

  1. Ali S, Metzger D, Bornert JM, Chambon, P. (1993) Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region. EMBO J 12: 1153–60PubMedGoogle Scholar
  2. Anonymous (1992) Breast cancer prevention trial will recruit 16 000 women. Oncology (Williston Park) 6: 57–58Google Scholar
  3. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS (1997) AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277: 965–968PubMedCrossRefGoogle Scholar
  4. Berry M, Metzger D, Chambon P (1990) Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J 9: 2811–2818PubMedGoogle Scholar
  5. Birkedal-Hansen H, Moore W, Bodden M, Windsor L, Birkedal-Hansen B, De-Carlo A, Engler J (1993) Matrix metalloproteases; a review. Oral Biol Med 4: 197–250Google Scholar
  6. Cavaillès V, Dauvois S, Danielian PS, Parker MG (1994) Interaction of proteins with transcriptionally active estrogen receptors. Proc Natl Acad Sci USA 91: 10009–10013PubMedCrossRefGoogle Scholar
  7. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM. (1997) Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell 90: 569–580PubMedCrossRefGoogle Scholar
  8. Dauvois S, Danielian PS, White R, Parker, MG (1992) Antiestrogen ICI 164,384 reduces cellular estrogen receptor content by increasing its turnover. Proc Natl Acad Sci USA 89: 4037–41PubMedCrossRefGoogle Scholar
  9. Dotzlaw H, Leygue E, Watson PH, Murphy LC (1997) Expression of estrogen receptor-beta in human breast tumors. J Clin Endocrinol Metab 82: 2371–2374PubMedCrossRefGoogle Scholar
  10. Gaub MP, Bellard M, Scheuer I, Chambon P, Sassone-Corsi P (1990) Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex. Cell 6: 1267–1276CrossRefGoogle Scholar
  11. Green S (1990) Modulation of oestrogen receptor activity by oestrogens and anti-oestrogens. J Steroid Biochem Mol Biol 37: 747–751PubMedCrossRefGoogle Scholar
  12. Gronemeyer H, Benhamou B, Berry M, Bocquel MT, Gofflo D, Garcia T, Lerouge T, Metzger D, Meyer ME, Tora L, Vergezac A and Chambon P (1992) Mechanisms of Antihormone Action. J Steroid Biochem Mol Biol 41: 217–221PubMedCrossRefGoogle Scholar
  13. Hong H, Kohli K, Trivedi A, Johnson DL, Stallcup M R (1996) GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc Natl Acad Sci USA 93: 4948–4952PubMedCrossRefGoogle Scholar
  14. Horwitz KB (1994) How do breast cancers become hormone resistant? J Steroid Biochem Mol Biol 49: 295–302PubMedCrossRefGoogle Scholar
  15. Huynh HT, Pollak M (1993) Insulin-like growth factor I gene expression in the uterus is stimulated by tamoxifen and inhibited by the pure antiestrogen ICI 182780. Cancer Res 23: 5585–5588Google Scholar
  16. Jamil A, Croxtall JD, White J O (1991) The effect of anti-oestrogens on cell growth and progesterone receptor concentration in human endometrial cancer cells ( Ishikawa ). J Mol Endocrinol 6: 215–21Google Scholar
  17. Jordan VC (1992) The strategic use of antiestrogens to control the development and growth of breast cancer. Cancer 70: 977–982PubMedGoogle Scholar
  18. Katzenellenbogen BS, Korach KS (1997) Editorial: a new actor in the estrogen receptor drama — enter ER beta. Endocrinology 138: 861–862PubMedCrossRefGoogle Scholar
  19. Katzenellenbogen JA, O’Malley BW, Katzenellenbogen BS (1996) Tripartite steroid hormone receptor pharmacology: interaction with multiple effector sites as a basis for the cell-and promoter-specific action of these hormones. Mol Endocrinol 10: 119–131PubMedCrossRefGoogle Scholar
  20. Kedar RP, Boume TH, Powles TJ, Collins WP, Ashley SE, Cosgrove DO, Campbell S (1994) Effects of tamoxifen on uterus and ovaries of post menopausal women in a randomised breast cancer prevention trial. Lancet 343: 1318–21PubMedCrossRefGoogle Scholar
  21. Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996) Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93: 5925–5930.PubMedCrossRefGoogle Scholar
  22. Leitman DC, Ribeiro RCJ, Mackow ER, Baxter JD, West BL (1991) Identification of a tumor necrosis factor-responsive element in the tumor necrosis factor alpha gene. J Biol Chem 266: 9343–9346PubMedGoogle Scholar
  23. Li H, Gomes Pi, Chen JD (1997) RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proc Natl Acad Sci USA 94: 8479–8484PubMedCrossRefGoogle Scholar
  24. McDonnell DP, Clemm DL, Hermann T, Goldman ME, Pike JW (1995) Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol 9: 659–69PubMedCrossRefGoogle Scholar
  25. Montano MM, Katzenellenbogen BS (1997) Identification of a novel cis-acting element in the promoter of an estrogen-responsive gene that modulates sensitivity to hormone and antihormone. Proc Natl Acad Sci USA 94: 2581–2585PubMedCrossRefGoogle Scholar
  26. Morrow M, Jordan VC (1993) Molecular mechanisms of resistance to tamoxifen therapy in breast cancer. Arch Surg 128: 1187–1191PubMedCrossRefGoogle Scholar
  27. Mosselman S, Polman J, Dijkema R (1996) ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 392: 49–53PubMedCrossRefGoogle Scholar
  28. Onate SA, Tsai SY, Tsai MJ, O’Malley BW (1995) Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270: 1354–7PubMedCrossRefGoogle Scholar
  29. Onoe Y, Miyaura C, Ohta H, Nozawa S, Suda T (1997) Expression of estrogen receptor beta in rat bone. Endocrinology 138: 4509–4512PubMedCrossRefGoogle Scholar
  30. Paech K, Webb P, Kuiper GGJM, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS (1997) Differential ligand activation of estrogen receptors ER alpha and ER beta at AP1 sites. Science 277: 1508–1510PubMedCrossRefGoogle Scholar
  31. Parker MG (1990) Mechanisms of action of steroid receptors in the regulation of gene transcription. J Reprod Fertil 2: 717–720Google Scholar
  32. Philips A, Chalbos D, Rochefort H (1993) Estradiol increases and anti-estrogens antagonize the growth factor-induced activator protein-1 activity in MCF7 breast cancer cells without affecting c-fos and c-jun synthesis. J Biol Chem 268: 14103–14108PubMedGoogle Scholar
  33. Rajabi M, Solomon S, Poole AR (1991) Hormonal regulation of interstitial collagenase in the uterine cervix of pregnant guinea pig. Endocrinology 128: 863–871PubMedCrossRefGoogle Scholar
  34. Rodgers WH, Matrisian LM, Guidice LC, Dsupin B, Cannon P, Svitek C, Gor-stein F, Osteen KG (1994) Patterns of metalloprotease expression in cycling emdometrium imply differential functions and regulation by steroid hormones. J Clin Invest 94: 946–953PubMedCrossRefGoogle Scholar
  35. Tora L, Gaub MP, Mader S, Dierich A, Bellard M, Chambon P (1988) Cell-specific activity of a GGTCA half-palindromic oestrogen-responsive element in the chicken ovalbumin gene promoter. EMBO J 12: 3771–3778Google Scholar
  36. Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, Rosenfeld MG (1997) The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 387: 677–684PubMedCrossRefGoogle Scholar
  37. Tremblay GB, Tremblay A, Copeland NG, Gilbert DJ, Jenkins NA, Labrie F, Giguere V (1997) Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol Endocrinol 11: 353–365PubMedCrossRefGoogle Scholar
  38. Uht RM, Anderson CM, Webb P, Kushner PJ (1997) Transcriptional activities of estrogen and glucocorticoid receptors are functionally integrated at the AP-1 response element. Endocrinology 138: 2900–2908PubMedCrossRefGoogle Scholar
  39. Umayahara Y, Kawamori R, Watada H, Imano E, Iwama N, Morishima T, Yamasaki Y, Kajimoto Y, Kamada T (1994) Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer. J Biol Chem 269: 16433–16442PubMedGoogle Scholar
  40. Voegel JJ, Heine MJS, Zechel C, Chambon P, Gronemeyer H (1996) TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J 15: 3667–3675PubMedGoogle Scholar
  41. Wakeling AE (1993) The future of new pure antiestrogens in clinical breast cancer. Breast Cancer Res Treat 25: 1–9PubMedCrossRefGoogle Scholar
  42. Webb P, Lopez GN, Uht RM, Kushner PJ (1995) Tamoxifen activation of the estrogen receptor/AP- 1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol Endocrinol 9: 443–456PubMedCrossRefGoogle Scholar
  43. Yang NN, Venugopalan M, Hardikar S, Glasebrook A (1996) Identification of an estrogen response element activated by metabolites of 17-beta-estradiol and raloxifene. Science 273: 1222–1225PubMedCrossRefGoogle Scholar
  44. Zhou F, Bouillard B, Pharaboz-Joly MO, Andre J (1989) non-classical antiestrogenic actions of dexamethasone in variant MCF7 breast cancer cells in culture. Mol Cell Endocrinol 66: 189–197Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • P. Webb
  • M.-R. Keneally
  • J. Shinsako
  • R. Uht
  • C. Anderson
  • K. Paech
  • T. S. Scanlan
  • P. J. Kushner

There are no affiliations available

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