The Role of PKC in Retinoic Acid Regulation of Human Mammary Cancer Cell Proliferation.
Abstract
The data presented in this annual report (for award DAMDI7-96-I-6022) support our hypothesis for a mechanism of retinoic acid -induced growth arrest of human breast cancer cells. Specifically we believe that retinoic acid induced growth arrest of human breast cancer cells requires protein kinase Ca expression. The constitutive expression of PKCa in hormone independent, MDA-MB-231 cells induced retinoic acid sensitivity to inhibit the uncontrolled proliferation and to alter the proto-oncogene expression. Retinoic acid treatment in PKCa expressing MDA-MB-231 cells reduced 40% of cell proliferation and inhibited serum induction of c-fos expression. Concomitantly, c-jun expression was enhanced. These findings, along with the observation that retinoic acid treatment enhanced PKCa expression, conventional PKC activity and translocation of PKCa to cell membrane and nucleus, raised the possibility that PKCa induced retinoic acid sensitivity in MDA-MB-231 cells is caused by disturbance of mitogenic signaling or trancriptional regulation of target genes. By turning on/off the transcription of PKCa gene, we further demonstrated the PKCa regulation of c-fos and c-jun expression. In total, we demonstrate that the lack of anti-proliferation effect of retinoic acid in MDA-MB-231 cells is caused by the failure of RA induced PKCa expression and subsequent absence of PKCa altered gene expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA357326
Entities
People
- David A. Talmage
- Yunhi Cho
Organizations
- Columbia University