Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells (original) (raw)

Abstract

The androgen receptor (AR) is a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and prostate cell proliferation. Mutations or abnormal expression of AR in prostate cancer can play a key role in the process that changes prostate cancer from androgen-dependent to an androgen-independent stage. Using a yeast two-hybrid system, we were able to isolate a ligand-dependent AR-associated protein (ARA70), which functions as an activator to enhance AR transcriptional activity 10-fold in the presence of 10(-10) M dihydrotestosterone or 10(-9) M testosterone, but not 10(-6) M hydroxyflutamide in human prostate cancer DU145 cells. Our data further indicated that ARA70 Will only slightly induce the transcriptional activity of other steroid receptors such as estrogen receptor, glucocorticoid receptor, and progesterone receptor in DU145 cells. Together, these data suggest that AR may need a specific coactivator(s) such as ARA70 for optimal androgen activity.

5517

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson K. M., Liao S. Selective retention of dihydrotestosterone by prostatic nuclei. Nature. 1968 Jul 20;219(5151):277–279. doi: 10.1038/219277a0. [DOI] [PubMed] [Google Scholar]
  2. Bruchovsky N., Wilson J. D. The conversion of testosterone to 5-alpha-androstan-17-beta-ol-3-one by rat prostate in vivo and in vitro. J Biol Chem. 1968 Apr 25;243(8):2012–2021. [PubMed] [Google Scholar]
  3. Cato A. C., Skroch P., Weinmann J., Butkeraitis P., Ponta H. DNA sequences outside the receptor-binding sites differently modulate the responsiveness of the mouse mammary tumour virus promoter to various steroid hormones. EMBO J. 1988 May;7(5):1403–1410. doi: 10.1002/j.1460-2075.1988.tb02957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cavaillès V., Dauvois S., Danielian P. S., Parker M. G. Interaction of proteins with transcriptionally active estrogen receptors. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10009–10013. doi: 10.1073/pnas.91.21.10009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang C. S., Kokontis J., Liao S. T. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science. 1988 Apr 15;240(4850):324–326. doi: 10.1126/science.3353726. [DOI] [PubMed] [Google Scholar]
  6. Chang C., Da Silva S. L., Ideta R., Lee Y., Yeh S., Burbach J. P. Human and rat TR4 orphan receptors specify a subclass of the steroid receptor superfamily. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6040–6044. doi: 10.1073/pnas.91.13.6040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chang C., Saltzman A., Yeh S., Young W., Keller E., Lee H. J., Wang C., Mizokami A. Androgen receptor: an overview. Crit Rev Eukaryot Gene Expr. 1995;5(2):97–125. doi: 10.1615/critreveukargeneexpr.v5.i2.10. [DOI] [PubMed] [Google Scholar]
  8. Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5;377(6548):454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
  9. Durfee T., Becherer K., Chen P. L., Yeh S. H., Yang Y., Kilburn A. E., Lee W. H., Elledge S. J. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993 Apr;7(4):555–569. doi: 10.1101/gad.7.4.555. [DOI] [PubMed] [Google Scholar]
  10. Graham A., Hopkins B., Powell S. J., Danks P., Briggs I. Isolation and characterisation of the human lung NK-2 receptor gene using rapid amplification of cDNA ends. Biochem Biophys Res Commun. 1991 May 31;177(1):8–16. doi: 10.1016/0006-291x(91)91940-e. [DOI] [PubMed] [Google Scholar]
  11. Halachmi S., Marden E., Martin G., MacKay H., Abbondanza C., Brown M. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. Science. 1994 Jun 3;264(5164):1455–1458. doi: 10.1126/science.8197458. [DOI] [PubMed] [Google Scholar]
  12. Ham J., Thomson A., Needham M., Webb P., Parker M. Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus. Nucleic Acids Res. 1988 Jun 24;16(12):5263–5276. doi: 10.1093/nar/16.12.5263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hörlein A. J., När A. M., Heinzel T., Torchia J., Gloss B., Kurokawa R., Ryan A., Kamei Y., Söderström M., Glass C. K. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995 Oct 5;377(6548):397–404. doi: 10.1038/377397a0. [DOI] [PubMed] [Google Scholar]
  14. Lee J. W., Ryan F., Swaffield J. C., Johnston S. A., Moore D. D. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. Nature. 1995 Mar 2;374(6517):91–94. doi: 10.1038/374091a0. [DOI] [PubMed] [Google Scholar]
  15. Lubahn D. B., Joseph D. R., Sullivan P. M., Willard H. F., French F. S., Wilson E. M. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science. 1988 Apr 15;240(4850):327–330. doi: 10.1126/science.3353727. [DOI] [PubMed] [Google Scholar]
  16. Mizokami A., Yeh S. Y., Chang C. Identification of 3',5'-cyclic adenosine monophosphate response element and other cis-acting elements in the human androgen receptor gene promoter. Mol Endocrinol. 1994 Jan;8(1):77–88. doi: 10.1210/mend.8.1.8152432. [DOI] [PubMed] [Google Scholar]
  17. Oñate S. A., Tsai S. Y., Tsai M. J., O'Malley B. W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 1995 Nov 24;270(5240):1354–1357. doi: 10.1126/science.270.5240.1354. [DOI] [PubMed] [Google Scholar]
  18. Santoro M., Dathan N. A., Berlingieri M. T., Bongarzone I., Paulin C., Grieco M., Pierotti M. A., Vecchio G., Fusco A. Molecular characterization of RET/PTC3; a novel rearranged version of the RETproto-oncogene in a human thyroid papillary carcinoma. Oncogene. 1994 Feb;9(2):509–516. [PubMed] [Google Scholar]