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.