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ERα and ERβ expression and transcriptional activity are differentially regulated by HDAC inhibitors

Abstract

The proliferative action of ERα largely accounts for the carcinogenic activity of estrogens. By contrast, recent data show that ERβ displays tumor-suppressor properties, thus supporting the interest to identify compounds that could increase its activity. Here, we show that histone deacetylase inhibitors (HDI) upregulated ERβ protein levels, whereas it decreased ERα expression. Part of this regulation took place at the mRNA level through a mechanism independent of de novo protein synthesis. In addition, we found that, in various cancer cells, the treatment with different HDI enhanced the ligand-dependent activity of ERβ more strongly than that of ERα. On the other hand, in MDA-MB231 and HeLa cells, the expression of ERs modified the transcriptional response to HDI. The use of deletion mutants of both receptors demonstrated that AF1 domain of the receptors was required. Finally, we show that ERβ expression led to a dramatic increased in the antiproliferative activity of HDI, which correlated with a modification of the transcription of genes involved in cell cycle control by HDI. Altogether, these data demonstrate that the interference of ERβ and HDAC on the control of transcription and cell proliferation constitute a promising approach for cancer therapy.

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Abbreviations

ER:

estrogen receptor

HDAC:

histone deacetylase

HDI:

histone deacetylase inhibitor

E2:

17β-estradiol

References

  • Campbell-Thompson M, Lynch IJ, Bhardwaj B . (2001). Cancer Res 61: 632–640.

  • Cheng J, Lee EJ, Madison LD, Lazennec G . (2004). FEBS Lett 566: 169–172.

  • Cheung E, Schwabish MA, Kraus WL . (2003). EMBO J 22: 600–611.

  • Cohen LA, Amin S, Marks PA, Rifkind RA, Desai D, Richon VM . (1999). Anticancer Res 19: 4999–5005.

  • Cowley SM, Parker MG . (1999). J Steroid Biochem Mol Biol 69: 165–175.

  • de Cremoux P, Tran-Perennou C, Elie C, Boudou E, Barbaroux C, Poupon MF et al. (2002). Biochem Pharmacol 64: 507–515.

  • Doetzlhofer A, Rotheneder H, Lagger G, Koranda M, Kurtev V, Brosch G et al. (1999). Mol Cell Biol 19: 5504–5511.

  • Fajas L, Egler V, Reiter R, Miard S, Lefebvre AM, Auwerx J . (2003). Oncogene 22: 4186–4193.

  • Fu M, Wang C, Reutens AT, Wang J, Angeletti RH, Siconolfi-Baez L et al. (2000). J Biol Chem 275: 20853–20860.

  • Harrington WR, Sheng S, Barnett DH, Petz LN, Katzenellenbogen JA, Katzenellenbogen BS . (2003). Mol Cell Endocrinol 206: 13–22.

  • He TC, Zhou S, da Costa LT, Yu J, Kinzler KW, Vogelstein B . (1998). Proc Natl Acad Sci USA 95: 2509–2514.

  • Henderson BE, Ross R, Bernstein L . (1988). Cancer Res 48: 246–253.

  • Jang ER, Lim SJ, Lee ES, Jeong G, Kim TY, Bang YJ et al. (2004). Oncogene 23: 1724–1736.

  • Kramer OH, Gottlicher M, Heinzel T . (2001). Trends Endocrinol Metab 12: 294–300.

  • Lazennec G, Bresson D, Lucas A, Chauveau C, Vignon F . (2001). Endocrinology 142: 4120–4130.

  • Liu Z, Wong J, Tsai SY, Tsai MJ, O’Malley BW . (1999). Proc Natl Acad Sci USA 96: 9485–9490.

  • Margueron R, Duong V, Castet A, Cavaillès V . (2004). Biochem Pharmacol 68: 1239–1246.

  • Margueron R, Licznar A, Lazennec G, Vignon F, Cavailles V . (2003). J Endocrinol 179: 41–53.

  • Marks PA, Richon VM, Rifkind RA . (2000). J Natl Cancer Inst 92: 1210–1216.

  • McInerney EM, Weis KE, Sun J, Mosselman S, Katzenellenbogen BS . (1998). Endocrinology 139: 4513–4522.

  • McKenna NJ, O’Malley BW . (2002). Endocrinology 143: 2461–2465.

  • Minucci S, Horn V, Bhattacharyya N, Russanova V, Ogryzko VV, Gabriele L et al. (1997). Proc Natl Acad Sci USA 94: 11295–11300.

  • Paruthiyil S, Parmar H, Kerekatte V, Cunha GR, Firestone GL, Leitman DC . (2004). Cancer Res 64: 423–428.

  • Pettersson K, Gustafsson JA . (2001). Annu Rev Physiol 63: 165–192.

  • Pujol P, Rey JM, Nirde P, Roger P, Gastaldi M, Laffargue F et al. (1998). Cancer Res 58: 5367–5373.

  • Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P, Rochefort H . (2001). Cancer Res 61: 2537–2541.

  • Ruh MF, Tian S, Cox LK, Ruh TS . (1999). Endocrine 11: 157–164.

  • Sambucetti LC, Fischer DD, Zabludoff S, Kwon PO, Chamberlin H, Trogani N et al. (1999). J Biol Chem 274: 34940–34947.

  • Shang Y, Myers M, Brown M . (2002). Mol Cell 9: 601–610.

  • Sharma D, Blum J, Yang X, Beaulieu N, Macleod AR, Davidson NE . (2005). Mol Endocrinol 19: 1740–1751.

  • Stanley F, Samuels HH . (1984). J Biol Chem 259: 9768–9775.

  • Stevens MS, Aliabadi Z, Moore MR . (1984). Biochem Biophys Res Commun 119: 132–138.

  • Vigushin DM, Ali S, Pace PE, Mirsaidi N, Ito K, Adcock I et al. (2001). Clin Cancer Res 7: 971–976.

  • Vigushin DM, Coombes RC . (2002). Anticancer Drugs 13: 1–13.

  • Wang C, Fu M, Angeletti RH, Siconolfi-Baez L, Reutens AT, Albanese C et al. (2001). J Biol Chem 276: 18375–18383.

  • Yang X, Ferguson AT, Nass SJ, Phillips DL, Butash KA, Wang SM et al. (2000). Cancer Res 60: 6890–6894.

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Acknowledgements

We are grateful to S Bonnet and A Lucas for their technical help. We thank the Vector Core of the University Hospital of Nantes supported by the Association Française contre les Myopathies (AFM) for the production of Adenoviruses. This work was supported by grants from ARC (Association pour la Recherche contre le Cancer, Grant No. 3582; La ligue Nationale Contre le Cancer and from the National Institutes of Health (NIH CA18119). VD, RM and AL were recipient from the French Minister of Research. AL was also supported by the Ligue Nationale Contre le Cancer.

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Correspondence to V Cavaillès or G Lazennec.

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Duong, V., Licznar, A., Margueron, R. et al. ERα and ERβ expression and transcriptional activity are differentially regulated by HDAC inhibitors. Oncogene 25, 1799–1806 (2006). https://doi.org/10.1038/sj.onc.1209102

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