Nuclear Matrix Proteins in Disparity of Prostate Cancer
Abstract
African Americans(AA) have twice the incidence and mortality of prostate (PC) than Caucasian Americans (CA). While the disproportionate burden was partially explained by genetic, socioeconomic, and environmental factors, racial variation in the biology of prostate tumors was not investigated. We employed an unbiased functional genomics approach to identify genes differentially expressed in freshly procured prostate tumor cells of age- and tumor grade-matched AA and CA men. Microdissected (LCM)-procured in vivo-derived genetic materials of matched normal epithelium and PC cells were subjected to suppressive subtractive hybridization (SSH) to construct microarray chips encompassing two sets of race-based, PC-specific cDNAs. We demonstrate selective expression of the nuclear matrix proteins heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) and scaffold attachment factor B2 (SAFB2) in PC cells that correlate with disease progression and poor prognosis in AA men. SAFB2 and hnRNP H1 promote growth of PC cells via diverse mechanisms. Functional studies demonstrate that hnRNP H1 physically interacts with and induces AR transactivation in hormone dependent and independent manner. As an ER co-repressor, SAFB2 potentially paves the way for activation of E2-ER axis, which inturn promotes tumor growth through activation of AR signaling under hormone deprivation conditions. Our findings support a model in which hnRNPH1 is an auxiliary novel coactivator for AR and that activation of E2-ER axis in prostate tumors is a poor prognostic indicator of disease progression and survival. Collectively, both SAFB2 and hnRNPH1 have potential clinical utility as biomarkers, prognostic indicators and/or therapeutic targets in advanced PC, especially among AA-men.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2013
- Accession Number
- ADA602404
Entities
People
- Asim B. Abdel-mageed
Organizations
- Tulane University of Louisiana