1287 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN H1 CONFERS TRANSCRIPTION AND TRANSACTIVATION OF ANDROGEN RECEPTOR: IMPLICATIONS FOR DISEASE PROGRESSION IN AFRICAN AMERICAN MEN

You have accessJournal of UrologyProstate Cancer: Basic Research VII1 Apr 20101287 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN H1 CONFERS TRANSCRIPTION AND TRANSACTIVATION OF ANDROGEN RECEPTOR: IMPLICATIONS FOR DISEASE PROGRESSION IN AFRICAN AMERICAN MEN Yijun Yang, Dingwu Jia, Rodney Davis, Sudesh Strivastav, Krishnarao Moparty, Raju Thomas, Krzysztof Moroz, Byron Crawford, and Asim Abdel-Mageed Yijun YangYijun Yang New Orleans, LA More articles by this author , Dingwu JiaDingwu Jia New Orleans, LA More articles by this author , Rodney DavisRodney Davis Nashville, TN More articles by this author , Sudesh StrivastavSudesh Strivastav New Orleans, LA More articles by this author , Krishnarao MopartyKrishnarao Moparty New Orleans, LA More articles by this author , Raju ThomasRaju Thomas New Orleans, LA More articles by this author , Krzysztof MorozKrzysztof Moroz New Orleans, LA More articles by this author , Byron CrawfordByron Crawford New Orleans, LA More articles by this author , and Asim Abdel-MageedAsim Abdel-Mageed New Orleans, LA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.871AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES African American men (AA) have twice the incidence and mortality of prostate cancer (CaP) than Caucasian American (CA) men and men of other ethnic minority groups. The causes of this ethnic disparity in clinical manifestation and outcome of the disease are not well understood. METHODS We identified selective expression of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) in prostate tumor cells of AA men in comparison to CA men by employing a combined approach of laser capture microdissected (LCM), suppressive subtractive hybridization (SSH), and custom race-based CaP cDNA microarray on fresh specimens. Quantitative RT-PCR and ethnicity-based tissue microarray (TMA) analyses revealed selective nuclear accumulation of hnRNPH1 in tumor cells compared to adjacent normal epithelium and benign prostatic hyperplasia (BPH). RESULTS In addition to selective expression, hnRNPH1 up-regulates transcription, physically interacts with, and confers hormone-dependent (HD) and independent (HI) transactivation of androgen receptor (AR) in CaP cells. Further, our reporter, ChIP, and EMSA analyses demonstrate that hnRNPH1 binds to androgen response elements (AREs) on promoter and enhancer elements of PSA gene and the ligand binding domain-encoding exons D, E, and H of the AR gene, suggesting it acts as a coactivator of AR in CaP cells. Interestingly, siRNA silencing of hnRNPH1caused growth arrest and enhanced cytotoxicty of Bicalutamide in AR-expressing PC cells. CONCLUSIONS Our findings support a model in which hnRNP H1 is an exclusive auxiliary factor for AR to elicit androgen-specific transcriptional regulation of androgen-regulated genes and development of drug resistance. Given heterogeneity of CaP and that AR is implicated in androgen independent progression of CaP, the results demonstrate a previously uncharacterized mechanism for AR-hnRNPH1 axis in disease progression and hormone refractory via enhancing HD and HI mediated transcription and transactivation of AR in a subset of prostate tumor cells in AA men. The results not only reveal racial differences in the biology of PC, but also provide, for the first time, a new frontier for the development of diagnostic, preventive, and/or targeted therapeutic strategies to circumvent disease progression in AA men. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e498 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yijun Yang New Orleans, LA More articles by this author Dingwu Jia New Orleans, LA More articles by this author Rodney Davis Nashville, TN More articles by this author Sudesh Strivastav New Orleans, LA More articles by this author Krishnarao Moparty New Orleans, LA More articles by this author Raju Thomas New Orleans, LA More articles by this author Krzysztof Moroz New Orleans, LA More articles by this author Byron Crawford New Orleans, LA More articles by this author Asim Abdel-Mageed New Orleans, LA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...