A Novel Anti-Beta2-Microglobulin Antibody Inhibition of Androgen Receptor Expression, Survival, and Progression in Prostate Cancer Cells
Annual rept. 1 May 2008-30 Apr 2009
EMORY UNIV ATLANTA GA
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Beta2-microglobulin beta2M is a signaling and growth-promoting factor stimulating prostate cancer cell proliferation and progression. Blockade of the beta2M signaling axis resulted in the inhibition of androgen receptor AR and its target gene, prostate-specific antigen PSA, and the induction of programmed death of prostate cancer cells through activation of a caspase-dependent pathway in vitro and in vivo. In this annual summary report, we identified a cis-acting element, sterol regulatory element-binding protein-1 SREBP-1 binding site, within the 5-flanking human AR promoter region and its binding transcription factor, SREBP-1, regulating AR transcription by a new agent, anti-beta2M monoclonal antibody beta2M mAb, in prostate cancer cells using the promoter deletion assay, electrophoretic mobility shift assay EMSA and chromatin immunoprecipitation assay ChIP. The functional study of SREBP-1 revealed that knocked-down or overexpressed SREBP-1 utilizing a sequence-specific siRNA or an expression vector showed to decrease or increase total and nuclear AR proteins and cell viability in prostate cancer cells. These results provided a new concept to reveal the role of beta2M and its related signaling pathways in regulation of AR expression, cell proliferation, survival progression of human prostate cancers.
- Medicine and Medical Research