Protein kinase C (PKC) is a family of signal transduction proteins that regulate various fundamental cellular processes that are altered in tumors, including cell growth and survival. PKC signaling pathways are, therefore, attractive targets for therapeutic intervention in various cancers. PKC isozymes play a key role in maintenance of intestinal epithelial homeostasis, and altered expression profiles (e.g., loss of PKC alpha and delta, increased levels of PKC iota) have been identified in colon carcinomas. However, understanding of the role of alterations in PKC isozyme signaling in colon carcinogenesis is limited. Strategies are proposed to test the hypothesis that PKC alpha and iota are important survival factors in intestinal epithelial cells (IEC), and that PKC alpha signaling plays a key role in antagonizing the pro-apoptotic effects of PKC delta in this system. Proposed studies aim to (1) Use RNAi to determine the survival and pro-apoptotic signaling mechanisms of PKC alpha and PKC delta, respectively, (2) Determine if restoration of PKC delta expression in colon tumor cells lacking PKC alpha promotes/sensitizes these cells to apoptosis, and (3) Explore the role of PKC iota in survival of human colon tumor cells in the absence/presence of PKC delta expression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA113048-02
Application #
7097974
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2005-07-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263