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Estrogen-Receptor-Related Receptors and Hormone-Dependent Cancers

  • Olivia Lanvin
  • Stéphanie Bianco
  • Jean-Marc Vanacker
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Nuclear receptors (NRs) comprise a superfamily of ligand-dependent transcription factors that all share similar modular structures (1). A highly conserved DNA-binding domain (DBD), located toward the center of the NR, mediates recognition of specific response elements (REs) within the promoters of target genes. The C-terminus contains a less conserved ligand-binding domain (LBD), which is responsible for ligand-recognition, homo- or hetero-dimerization, interaction with co-modulators, and activation of target gene transcription. A number of NRs, termed “orphan” receptors, display features similar to those found in the “classical” (i.e., “liganded”) receptors, including a putative LBD, but for which no natural ligand has been characterized (2). Whether such ligands indeed exist, or whether orphan receptors can activate transcription in a constitutive manner is still subject to debate.

Keywords

Orphan Receptor Orphan Nuclear Receptor Lactoferrin Gene Constitutive Manner Specific Response Element 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Chambon P (2005) The nuclear receptor superfamily: a personal retrospect on the first two decades. Mol Endocrinol 19:1418–28.PubMedCrossRefGoogle Scholar
  2. 2.
    Giguère V (1999) Orphan nuclear receptors: from gene to function. Endocrine Rev 20: 689–725.CrossRefGoogle Scholar
  3. 3.
    Laudet V (1997) Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor. J Mol Endocrinol 19:207–26.PubMedCrossRefGoogle Scholar
  4. 4.
    Giguère V, Yang N, Segui P, et al. (1988) Identification for a new class of steroid hormone receptors. Nature 331:91–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Hong H, Yang L, Stallcup MR (1999) Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3. J Biol Chem 274:22618–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Bardet PL, Laudet V, Vanacker JM (2006) Studying non-mammalian models? Not a fool’s ERRand! Trends Endocrinol Metab 17:166–71.PubMedCrossRefGoogle Scholar
  7. 7.
    Luo J, Sladek R, Bader JA, et al. (1997) Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERRα. Nature 388:778–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Bonnelye E, Vanacker JM, Spruyt N, et al. (1997) Expression of the estrogen-related receptor 1 (ERR-1) orphan receptor during mouse development. Mech Dev 65:71–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Luo J, Sladek R, Carrier J, et al. (2003) Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor α. Mol Cell Biol 23:7947–56.PubMedCrossRefGoogle Scholar
  10. 10.
    Huss JM, Torra IP, Staels B, et al. (2004) Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol 24:9079–91.PubMedCrossRefGoogle Scholar
  11. 11.
    Schreiber SN, Knutti D, Brogli K, et al. (2003) The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha). J Biol Chem 278:9013–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Carrier JL, Deblois G, Champigny C, et al. (2004) Estrogen-related receptor α (ERRα) is a transcriptional regulator of apolipoprotein A-IV and controls lipid handling in the intestine. J Biol Chem 279:52052–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Schreiber SN, Emter R, Hock MB, et al. (2004) The estrogen-related receptor α (ERRα) functions in PPARgamma coactivator 1-α (PGC1-α)-induced mitochondrial biogenesis. Proc Natl Acad Sci USA 101:6472–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Bonnelye E, Aubin JE (2005) Estrogen receptor-related receptor alpha: a mediator of estrogen response in bone. J Clin Endocrinol Metab 90:3115–21.PubMedCrossRefGoogle Scholar
  15. 15.
    Bardet PL, Horard B, Laudet V, et al. (2005) The ERRalpha orphan nuclear receptor controls morphogenetic movements during zebrafish gastrulation. Dev Biol 281:102–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Susens U, Hermans-Borgmeyer I, Borgmeyer U (2000) Alternative splicing and expression of the mouse estrogen receptor-related receptor gamma. Biochem Biophys Res Commun 2000 267:532–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Horard B, Vanacker JM (2003) Estrogen receptor-related receptors: orphan receptors desperately seeking a ligand. J Mol Endocrinol 31:349–57.PubMedCrossRefGoogle Scholar
  18. 18.
    Greschik H, Wurtz JM, Sanglier S, et al. (2002) Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell 9:303–313.PubMedCrossRefGoogle Scholar
  19. 19.
    Kallen J, Schlaeppi JM, Bitsch F (2004) Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor α (ERRα): crystal structure of ERRα ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1α. J Biol Chem 279:49330–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Coward P, Lee D, Hull MV, et al. (2001) 4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor gamma. Proc Natl Acad Sci USA 98:8880–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Tremblay GB, Kunath T, Bergeron D, et al. (2001) Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERRβ. Genes Dev 15:833–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Suetsugi M, Su L, Karlsberg K, et al. (2003) Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors. Mol Cancer Res 1:981–91.PubMedGoogle Scholar
  23. 23.
    Willy PJ, Murray IR, Qian J, et al. (2004) Regulation of PPARγ coactivator 1α (PGC-1α) signaling by an estrogen-related receptor α (ERRα) ligand. Proc Natl Acad Sci USA 101:8912–17.PubMedCrossRefGoogle Scholar
  24. 24.
    Laganière J, Tremblay GB, Dufour CR, et al. (2004) A polymorphic autoregulatory hormone response element in the human estrogen-related receptor alpha (ERRα) promoter dictates peroxisome proliferator-activated receptor γ coactivator-1α control of ERRα expression. J Biol Chem 279:18504–10.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang Z, Chen K, Shih JC, et al. (2006) Estrogen-related receptors-stimulated monoamine oxidase B promoter activity is down-regulated by estrogen receptors. Mol Endocrinol 20:1547–61.PubMedCrossRefGoogle Scholar
  26. 26.
    Yang N, Shigeta H, Shi H, et al. (1996) Estrogen-related receptor, hERR1, modulates estrogen receptor mediated response of human lactoferrin gene promoter. J Biol Chem 271:5795–804.PubMedCrossRefGoogle Scholar
  27. 27.
    Johnston SD, Liu X, Zuo F, et al. (1997) Estrogen-related receptor α 1 functionally binds as a monomer to extended half-site sequences including ones contained within estrogen-response elemens. Mol Endocrinol 11:342–52.PubMedCrossRefGoogle Scholar
  28. 28.
    Bonnelye E, Vanacker JM, Dittmar T, et al. (1997) The ERR-1 orphan receptor is a transcriptional activator expressed during bone development. Mol Endocrinol 11:905–16.PubMedCrossRefGoogle Scholar
  29. 29.
    Vanacker JM, Pettersson K, Gustafsson JA, et al. (1999) Transcriptional targets shared by estrogen-receptor-related receptors (ERRs) and estrogen receptor (ER)α, but not ERβ. EMBO J 18:4270–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Pettersson K, Svensson K, Mattsson R, et al. (1996) Expression of a novel member of estrogen response element-binding nuclear receptors is restricted to the early stages of chorion formation during mouse embryogenesis. Mech Dev 54:211–23.PubMedCrossRefGoogle Scholar
  31. 31.
    Kraus KJ, Ariazi EA, Farrell ML, et al. (2002) Estrogen-related receptor alpha-1 actively antagonizes estrogen-receptor regulated transcription in MCF-7 mammary cells. J Biol Chem 277:24826–34.PubMedCrossRefGoogle Scholar
  32. 32.
    Lu D, Kiriyama Y, Lee KY, et al. (2001) Transcriptional regulation of the estrogen-inducible pS2 breast cancer marker gene by the ERR family of orphan nuclear receptors. Cancer Res 61:6755–61.PubMedGoogle Scholar
  33. 33.
    Seely J, Amigh KS, Suzuki T, et al. (2005) Transcriptional regulation of dehydroepiandrosterone sulfotransferase (SULT2A1) by estrogen-related receptor alpha. Endocrinology 146:3605–13.PubMedCrossRefGoogle Scholar
  34. 34.
    Yang C, Zhou D, Chen S (1998) Modulation of aromatase expression in the breast tissue by ERRα-1 orphan receptor. Cancer Res 58:5696–700.Google Scholar
  35. 35.
    Shigeta H, Zuo W, Yang N, et al. (1997) The mouse estrogen-receptor related orphan receptor α 1: molecular cloning and estrogen responsiveness. J Mol Endocrinol 19:299–309.PubMedCrossRefGoogle Scholar
  36. 36.
    Nelson PS, Clegg N, Arnold H, et al. (2002) The program of androgen-responsive genes in neoplastic prostate epithelium. Proc Natl Acad Sci USA 99:11890–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Ariazi EA, Jordan VC (2006) Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Topics Med Chem 6:181–93.CrossRefGoogle Scholar
  38. 38.
    Cavallini A, Notarnicola M, Giannini R, et al. (2005) Oestrogen receptor-related receptor alpha (ERRα) and oestrogen receptors (ERα and ERβ) exhibit different gene expression in human colorectal tumor progression. Eur J Cancer 41:1487–1494.PubMedCrossRefGoogle Scholar
  39. 39.
    Cheung CP, Yu S, Wong KB, et al. (2005) Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues. J Clin Endocrinol Metab 90:1830–44.PubMedCrossRefGoogle Scholar
  40. 40.
    Sun P, Sehouli J, Denkert C, et al. (2005) Expression of estrogen receptor-related receptors, a subfamily of orphan nuclear receptors, as new tumor biomarkers in ovarian cancer cells. J Mol Med 83: 457–67.PubMedCrossRefGoogle Scholar
  41. 41.
    Ariazi EA, Clark GM, Mertz JE (2002) Estrogen-related receptor α and estrogen-related receptor γ associate with unfavorable and favorable biomarkers, respectively, in human breast cancer. Cancer Res 62:6510–6518.PubMedGoogle Scholar
  42. 42.
    Suzuki T, Miki Y, Moriya T, et al. (2004) Estrogen-related receptor α in human breast carcinoma as a potent prognostic factor. Cancer Res 64: 4670–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Castet A, Herledan A, Bonnet S, et al. (2006) Receptor-interacting protein 140 differentially regulates estrogen receptor-related receptor transactivation depending on target genes. Mol Endocrinol 20: 1035–47.PubMedCrossRefGoogle Scholar
  44. 44.
    Barry JB, Giguère V (2005) Epidermal growth factor-induced signaling in breast cancer cells results in selective target gene activation by orphan nuclear receptor estrogen-related receptor alpha. Cancer Res 65:6120–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Olivia Lanvin
  • Stéphanie Bianco
  • Jean-Marc Vanacker
    • 1
  1. 1.INSERM EMI 229 Centre de Recherche en CancerologieMontpellierFrance

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