Androgen Receptor-Target Genes in African American Prostate Cancer Disparities

Prostate cancer has higher incidence and mortality rates among African Americans (AA) compared with Caucasian Americans (CA). In order to explore the mechanism of this prostate cancer disparity at molecular level, we used an integrative approach, which combines gene expression profiling, promoter analysis and well as functional screens to study the differential transcriptions and deregulated signaling pathways in AA versus CA prostate cancers. A previous microarray assay has shown that 1188 genes are differentially expressed in AA prostate cancers. Our gene promoter analysis revealed that 382 genes out of 1188 genes contain at least one androgen receptor (AR) binding site on the promoter region and all these genes are converged on the androgen receptor pathway, which addressed the AR as a critical oncogenic molecule in AA prostate cancer. Meanwhile, STAT1, RHOA, ITGB5, MAPKAPK2, CSNK2A1 and PIK3CB were confirmed by chromatin immunorecipitation assay as novel AR-target genes in prostate cancer disparity. Furthermore, androgen stimulation by dihydrotestosterone as well as the invasion assay demonstrated that androgen stimulation could increase AR binding and the transcriptional expression of RHOA, ITGB5 and PIK3CB genes, as well as the invasive activity of AA prostate cancer cells. Taken together, our findings provide the first evidence of multiple cancer-associated pathways converging on AR signaling, which might be due to AR-target genes activation and invasion of prostate cancer cells in AAs compared to CAs.

Author

• YANG, QI

Language

• en

Date created

• 2013

Type of Work

• Master's Thesis

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Biochemistry and Molecular Biology

Degree

• M.S.

Advisor

• Lee, Norman H.

Committee Member(s)

• Vanderhoek, Jack Y.

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/xk81jk655