Accession Number:

ADA543823

Title:

Modulation of Beta-Catenin Activity with PKD1 in Prostate Cancer

Descriptive Note:

Final rept. 1 Apr 2008-31 Mar 2011

Corporate Author:

SANFORD RESEARCH SIOUX FALLS SD

Personal Author(s):

Report Date:

2011-04-01

Pagination or Media Count:

16.0

Abstract:

During the 2010-11 funding cycle we have made significant progress on our project. We have published ten papers and fourteen abstracts. In addition to publications, we have obtained collaborative grants from the state Governors 2010 initiative, NIH NCI RO1 and pharmaceutical industries Merck Pharmaceuticals, Investigator Initiated Grant. We have used transiently transfected C4-2 cell lines to investigate the effect of PKD mutants on the various aspects of cellular functions including cell proliferation, colony formation and motility. The results from these experiments are presented below and provide promising results for further investigation. However, due to the low efficiency of transient transfection of C4-2 cells, we have decided to generate stably transfected C4-2 cell lines using retro-viral mediated transfection system to obtain reliable results. In this study cycle, we have generated retroviral PKD1 mutants in order to identify the domains involved in interaction and modulation of beta-catenin activity. The retroviral system is a well established technique that yields much higher efficiency of generation of stable transfect compared to cationic-lipid mediated transfection. We, in collaboration with Dr. Chauhan, have determined the effect of PKD1 on prostate tumor growth in a xenograft mouse model system. We have also determined the effect of Bryostatin-1 on apoptosis and chemo-sensitization. Additionally, we have also discovered a new modulator of PKD1, curcumin, a chemo-dietary agent. Results were presented at the DOD IMPACT and AACR 2011 meetings. Our work related to curcumin pre-treatment strategy of cancer cells induces chemoradiosensitivity in cancer cells has been published. Based on clinical implications of this novel strategy, this paper was selected for press release.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE