A Novel Anti-Beta2-Microglobulin Antibody Inhibition of Androgen Receptor Expression, Survival, and Progression in Prostate Cancer Cells
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 31, 2009
- Accession Number
- ADA503491
Entities
People
- Wen-chin Huang
Organizations
- Emory University