Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells Journal Article
| Authors: | Nwachukwu, J. C.; Mita, P.; Ruoff, R.; Ha, S.; Wang, Q.; Huang, S. J.; Taneja, S. S.; Brown, M.; Gerald, W. L.; Garabedian, M. J.; Logan, S. K. |
| Article Title: | Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells |
| Abstract: | The androgen receptor (AR) directs diverse biological pro-cesses through interaction with coregulators such as AR trapped clone-27 (ART-27). Our results show that ART-27 is recruited to AR-binding sites by chromatin immunoprecipi-tation analysis. In addition1 the effect of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are up-regulated upon ART-27 depletion include regulators of DNA damage check-point and cell cycle progression1 suggesting that ART-27 functions to keep expression levels of these genes low. Consistent with this idea, stable reduction of ART-27 by short-hairpin RNA enhances LNCaP cell proliferation com-pared with control cells. The effect of ART-27 loss was also examined in response to the antiandrogen bicalutamide.Unexpectedly, cells treated with ART-27 siRNA no longer exhibited gene repression in response to bicalutamide. To examine ART-27 loss in prostate cancer progression1 immu-nohistochemistry was conducted on a tissue array containing samples from primary tumors of individuals who were clinically followed and later shown to have either recurrent or nonrecurrent disease. Comparison of ART-27 and AR staining indicated that nuclear ART-27 expression was lost in the majority of AR-positive recurrent prostate cancers. Our studies show that reduction of ART-27 protein levels in prostate cancer may facilitate antiandrogen-resistant disease. ©2009 American Association for Cancer Research. |
| Keywords: | immunohistochemistry; controlled study; human tissue; protein expression; primary tumor; unclassified drug; human cell; genetics; androgen; cancer growth; recurrent cancer; protein function; neoplasm; cell proliferation; metabolism; dna damage; cell cycle progression; neoplasm recurrence, local; gene expression; cell growth; neoplasm proteins; genetic transcription; pathology; cell line, tumor; physiology; prostate cancer; prostatic neoplasms; gene expression regulation; gene expression regulation, neoplastic; biosynthesis; messenger rna; rna, messenger; tumor recurrence; cancer cell; prostate tumor; gene repression; cell growth processes; tumor protein; tumor cell line; drug response; staining; androgen antagonists; gene control; androgen receptor; upregulation; cell nucleus; antiandrogen; bicalutamide; receptors, androgen; tissue microarray; short hairpin rna; androgens; anilides; nitriles; tosyl compounds; nitrile; cell strain lncap; regulator protein; androgen receptor trapped clone 27; anilide; toluenesulfonic acid derivative; uxt protein, human; neoplasms, hormone-dependent |
| Journal Title: | Cancer Research |
| Volume: | 69 |
| Issue: | 7 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2009-04-01 |
| Start Page: | 3140 |
| End Page: | 3147 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-08-3738 |
| PUBMED: | 19318562 |
| PROVIDER: | scopus |
| PMCID: | PMC2702238 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "CODEN: CNREA" - "Source: Scopus" |
