A Novel Anti-Beta2-Microglobulin Antibody Inhibition of Androgen Receptor Expression, Survival, and Progression in Prostate Cancer Cells
Abstract
We previously demonstrated that a key lipogenic transcription factor, sterol regulatory element-binding protein-1 (SREBP-1), regulated androgen receptor (AR) transcriptional expression through AR promoter activity and cell growth in prostate cancer cells. In this annual summary report, we further investigate the molecular mechanism by which SREBP-1 promotes prostate cancer growth and progression, we manipulated permanent SREBP-1 expression in prostate cancer cells. Alteration of SREBP-1 expression leads to regulate AR expression, cell growth, migration and invasion in prostate cancer cells. SREBP-1 also showed to induce fatty acid and lipid formation in prostate cancer cells through increase of fatty acid synthase expression. Additionally, SREBP-1 induced oxidative stress and NADPH oxidase 5 (Nox5) expression in prostate cancer cells. In subcutaneous xenograft mouse models, SREBP-1 significantly increased LNCaP tumor burdens and promoted prostate tumor initiation. These findings reveal that the novel lipogenic mechanism by which SREBP-1 regulating AR activity, fatty acid and lipid biosynthesis, and oxidative stress contributes to prostate cancer growth and progression, and further provides a new potential target to prevent and treat prostate cancer malignancy.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2010
- Accession Number
- ADA545568
Entities
People
- Wen-chin Huang
Organizations
- Cedars-Sinai Medical Center