Identification of Retinoid Induced Growth Suppressing Genes
Abstract
Breast cancer is the leading cause of female cancer deaths in this country and the incidence of new cases continues to rise. Vitamin A status is a possible factor contributing to the development of many human cancers, including those of the breast. A major question regarding the role of vitamin A and breast cancer remains unanswered. How, on a molecular level, do retinoids induce growth arrest of hormone-dependent breast cancer cells? I 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'. 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. As a result of these studies we demonstrated that: (1) PKC-Alpha and PTP-1C are up-regulated in retinoid treated cells; (2) PKC-Alpha mediates the anti-proliferative action of retinoids in T47D cells; (3) PKC-Alpha cooperates with retinoids to limit the proliferation of the normally retinoid resistant cell line, MDA-MB-231. 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, 2000
- Accession Number
- ADA395643
Entities
People
- David A. Talmage
Organizations
- Columbia University