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. Laser capture 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 protein heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in nuclei of PC cells that correlate with disease progression and poor prognosis in AA men. hnRNP H1 siRNA silencing conferred growth arrest and sensitized androgen receptor (AR)-expressing PC cells to bicalutamide. Functional studies demonstrate that hnRNP H1 physically interacts with and induces AR transactivation in hormone dependent and independent manner. The transcriptional upregulation of AR and PSA genes by hnRNP H1 was coupled with an increase in AR binding to its cognate DNA element on PSA promoter and exonic domains within the AR gene. The findings support a model in which hnRNP H1 is an auxiliary coactivator for ligand-dependent and independent transactivation of AR in tumor cells. Our data further demonstrate a previously uncharacterized mechanism for AR-hnRNP H1 axis in disease progression and development of hormone refractory PC in AA men.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA554015
Entities
People
- Asim B. Abdel-mageed
Organizations
- Tulane University of Louisiana