Abstract
Abstract The causes of ethnic disparity in the clinical manifestation and outcome of prostate cancer (CaP) are not well understood. African Americans (AA) have twice the incidence and mortality of CaP than Caucasian Americans (CA). We identified by a novel functional genomics approach, encompassing laser capture microdissection (LCM), suppressive subtractive hybridization (SSH) and custom race-based CaPspecific cDNA array chips, selective expression of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate tumor cells of AA in comparison to CA men. hnRNP H1 expression correlates with disease progression and score and poor prognosis in AA men. Subsequent functional studies demonstrate that hnRNP H1 up-regulates transcription, and physically interacts with, and confers hormone-dependent and independent transactivation of androgen receptor (AR) in CaP cells. In addition, hnRNP H1 enhances AR binding to its cognate DNA element on promoter and enhancer element of PSA gene and selective exonic domains of the AR gene. These findings support a model in which hnRNP H1 is an auxiliary coactivator for ligand-dependent and independent transactivation of AR in tumor cells. Furthermore, siRNA silencing of hnRNP H1 elicited growth arrest and enhanced cytotoxicity of antiandrogen bicalutamide in CaP cells. Our data support a new role for hnRNP H1 in ethnic disparity of CaP and further demonstrate a previously uncharacterized mechanism for AR-hnRNP H1 axis in disease progression and development of hormone refractory in AA men. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B58.
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