Cellular Retinoic Acid Binding Protein and Breast Cancer
Abstract
In attempts to understand how the signaling by retinoic acid (the active vitamin A metabolite) is regulated we have been studying the retinoic acid binding protein called CRABP-II. These studies revealed that CRABP-II acts to enhance the transcriptional activities of RA and that it does so by directly delivering the hormone to its cognate transcription factor, RAR. Consequently CRABP-II dramatically sensitized cultured mammary carcinoma cells to RA-induced growth inhibition. Similarly, over-expression of CRABP-II inhibited mammary tumor growth in two different mouse models of cancer. CRABP-II may be a novel target for therapeutic and preventive strategies for retinoid-treatment of breast cancer. This project aims to delineate the mechanism by which CRABP-II modulates RA activity, especially as related to its ability to enhance the anti-proliferative action of the ligand. The first aim is to determine the extent to which CRABP-II acts in activating different isotypes of RAR. The second aim is to dissect the mechanism by which RA-induced growth inhibition is mediated. This will then allow for closer inspection of particular target genes that are under such control. The third aim is to understand the basis for RA-resistance of mammary carcinoma cells and how CRABP-II functions to overcome this resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA425991
Entities
People
- Leslie J. Willmert
Organizations
- Cornell University