Modulation of Beta-catenin Activity with PKD1 in Prostate Cancer
Abstract
During the 2008-12 funding period we have made significant progress on our project. We have published 22 papers and 28 abstracts. In this study, we revealed functional aspects of role of -catenin signaling through PKD1 in prostate cancer. We have investigated novel mechanism of the suppression of -catenin transcriptional activity by PKD1 and its modulators such as Bryostatin 1 and Curcumin. Our studies also suggest that, Bryostatin-1, a PKD1 modulator, efficiently attenuates -catenin transcriptional activity and induces chemosensitization in prostate cancer cells. We identified the PKD1 domains involved in interaction and modulation of -catenin activity. We, in collaboration with Dr. Chauhan, have also developed a xenograft mouse model system with the highly metastatic C4-2 cell lines. Our experiments suggest that PKD1 expression inhibited prostate tumor growth in xenograft mouse model. In addition, we have investigated the effects of PKD1 overexpression on gene transcription using PCR microarray techniques. To determine the correlation of PKD1 expression with prostate cancer progression, we have processed 60 prostate cancer samples for PKD1 and -catenin staining. We have also revealed a novel curcumin pre-treatment strategy for inducing chemo/radio-sensitization of cancer cells. Based on clinical implications of this novel strategy, this study was published and selected for press release. All related studies have been presented at IMPACT and Annual American Association for Cancer Research (AACR) meetings. In addition to publications, we have obtained collaborative grants from the state (Governor s 2010 initiative), NIH (NCI RO1, NCRR COBRE) and pharmaceutical industries (Merck Pharmaceuticals, Investigator Initiated Grant).
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2012
- Accession Number
- ADA599991
Entities
People
- Meena Jaggi
- Subhash C. Chauhan