Androgen receptor-target genes in Afircan American prostate cancer disparities

Authors

Bi-Dar Wang, George Washington UniversityFollow
Qi Yang, George Washington University
Fernando Bianco, George Washington University
Ramez Andrawis, George Washington University
Thomas W. Jarrett, George Washington UniversityFollow
Harold A. Frazier, George Washington UniversityFollow
Steven R. Patierno, George Washington UniversityFollow
Norman H. Lee, George Washington UniversityFollow

Document Type

Journal Article

Publication Date

2013

Journal

Prostate Cancer

Inclusive Pages

Article ID 763569

Abstract

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter analysis revealed that 382 out of 1,188 genes contained cis-acting AR-binding sequences. Chromatin immunoprecipitation confirmed STAT1, RHOA, ITGB5, MAPKAPK2, CSNK2A,1 and PIK3CB genes as novel AR targets in PCa disparities. Moreover, functional screens revealed that androgen-stimulated AR binding and upregulation of RHOA, ITGB5, and PIK3CB genes were associated with increased invasive activity of AA PCa cells, as siRNA-mediated knockdown of each gene caused a loss of androgen-stimulated invasion. In summation, our findings demonstrate that transcriptional changes have preferentially occurred in multiple signaling pathways converging (“transcriptional convergence”) on AR signaling, thereby contributing to AR-target gene activation and PCa aggressiveness in AAs.

Comments

Reproduced with permission of Hindawi Publishing Corp. Prostate Cancer.

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

APA Citation

Wang, B.D., Yang, Q., Ceniccola, K., Bianco, K., Andrawis, R., Jarrett, T., Frazier, H., Patierno, S.R., Lee, N.H. (2013). Androgen receptor-target genes in Afircan American prostate cancer disparities. Prostate Cancer, 763569.

Peer Reviewed

1

Open Access

1