Suppression of Androgen Receptor Transactivation by Akt Kinase
Abstract
Data suggest androgen/androgen receptor (AR) may be involved in prostate cancer proliferation, but opposite roles of cell growth inhibition and apoptosis are documented. The detailed mechanism of how androgen/AR functions in apoptosis, remains unclear. Serine/threonine kinase (Akt) plays a role in promoting cell survival through anti-apoptotic effects. Akt was found active in prostate cancer LNCaP cells and plays an essential role for survival. Our preliminary data demonstrated Akt phosphorylates AR at Ser210 and Ser79O. Mutation at Ser210 results in reversion of Akt-mediated suppression of AR transactivation. Activation of phosphatidylinositol-3-OH kinase/Akt pathway results in the suppression of AR target genes. Our hypothesis is that Akt may control androgen/AR-induced apoptosis by phosphorylating and inhibiting AR. Our Akt studies led into study of PTEN pathway. We have shown via Pl3K/Akt-dependent pathway, PTEN regulates AR activity in high passage LNCaP cells and suppresses AR activity in the early passage LNCP cells; PI3k/Akt pathway promoted AR ubiquitylation, leading to AR degradation; and restoration of AR function or Pl3k/Akt pathway rescues cells from PTEN-induced apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA444244
Entities
People
- Chawnshang Chang
Organizations
- University of Rochester