Beta Catenin in Prostate Cancer Apoptosis
Abstract
During this funding period, we performed TRAIL-TZD-mediated apoptotic studies in androgen dependent (LNCaP and 22RV1) and androgen independent (DU145 and PC3) prostate cancer cells and the response was maximal in the LNCaP cells with 50 M TZD and 100ng/ml TRAIL combination. This apoptotic response is also associated with increased -catenin cleavage, indicating its potential role. Knockdown of -catenin expression and overexpression of -catenin modulated TRAIL-TZD-induced apoptosis. Studies with the cleaved -catenin protein revealed that this cleaved fragment losses interaction with TCF4, while retaining strong interaction with E-cadherin and -catenin. These indicated (i) a potential mechanism by which TRAIL-TZD antagonizes -catenin/TCF4-induced transcription and (ii) suggested that E-cadherin and -catenin interaction might be critical for apoptosis induction. Based on Mass Spec data various myc -catenin (D/A) mutants were created but they were unable to significantly antagonize -catenin cleavage and apoptosis. Studies also showed that GSK3 inhibition promotes TRAIL-induced apoptosis and TRAIL-TZD significantly reduces expression of GSK3 and increases pGSK3 Ser9 levels. In addition, this apoptosis pathway seems to involve AMPK, since AMPK-dominant negative (DN) overexpression significantly attenuates TRAIL-TZD-induced apoptosis and -catenin cleavage. The C42 and C42B cells showed significant apoptosis with TRAIL-TZD in vitro and C42 cells formed in vivo xenografts in nude mice. Treatment with TRAIL-TZD in vivo however, didn t show any significant effect on prostate tumor regression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2014
- Accession Number
- ADA609572
Entities
People
- Basabi Rana
Organizations
- Loyola University New Orleans