DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click
HERE to register or log in.
Accession Number:
ADA460064
Title:
Effect of Chimaerins, Novel Receptors for Phorbol Esters, on Breast Cancer Cell Proliferation and Cell Cycle Progression
Descriptive Note:
Annual summary rept. 1 Jul 2003-30 Jun 2006
Corporate Author:
PENNSYLVANIA UNIV PHILADELPHIA
Report Date:
2006-07-01
Pagination or Media Count:
46.0
Abstract:
Chimaerins are a family of intracellular receptors for the phorbol ester tumor promoters and the second messenger diacylglycerol. The discovery of chimaerins challenges the traditional view that protein kinase C is the only family of receptors for phorbol esters. This proposal was designed to investigate the biological functions of chimaerins. We found that 1 the mRNA levels of beta2-chimaerin, one of the most widely expressed chimaerin isoforms, were significantly lower in breast cancer cells and tissues than that in breast normal cells and tissues 2 re-expression of beta2-chimaerin or its catalytical domain beta-GAP using an adenoviral gene delivery technique induced cell cycle arrest at G1 phase and subsequently inhibited breast cancer cell proliferation 3 the effect of beta2- chimaerin on cell cycle progression and cell proliferation entirely depended on its Rac-GAP activity 4 heregulin beta1 HRG, an EGF-like growth factor and a mitogen for breast cancer cells, is a strong activator of Rac in breast cancer cells and promotes breast cancer cell proliferation through ErbB receptorsPI3KRacErk-dependent up-regulation of cyclin D1 and p21 expression 5 expression of beta2-chimaerin inhibited HRG-induced Rac activation and impaired Rac-dependent responses including cell migration, Erk12 activation, cyclin D1 and p21 expression, and cell proliferation. These findings suggest that beta2-chimaerin may act as a tumor suppressor.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE