Identification of Retinoid Induced Growth Suppressing Genes
Abstract
I had originally proposed to test the hypothesis that "biologically active derivatives of vitamin A (retinoids) inhibit mammary carcinoma cell proliferation by disrupting one or more growth factor activated serine/threonine protein kinase signaling cascades. Targets of these signaling cascades include genes that encode proteins required for progression through the cell cycle". The experimental approach was designed to identify the retinoid-regulated genes that negatively regulate cell cycle progression. Specifically, I proposed to identify and isolate genes whose expression is regulated by retinoic acid in hormone-dependent, but not hormone-independent cells, and determine if these genes encode proteins involved in cell cycle progression. To date we demonstrated that the alpha isoform of protein kinase C is retinoid induced in hormone dependent breast cancer cells and that the activity of this PKC is responsible for the retinoid-dependent disruption in mitogen signaling that results in growth arrest. The significance of this role of PKC% is underscored by our further finding that expression of PKCa in hormone-independent breast cancer cells allows retinoids to inhibit mitogenic signaling. In the long term, these results might open the door for developing combination therapy approaches that jointly target retinoid and PKC signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA382917
Entities
People
- David Talmagae
Organizations
- Columbia University