The Effects of Fatty Acids on Retinoid Signaling in Human Mammary Epithelial Cells and Breast Cancer Cells
Annual summary rept. 1 Sep 2004-31 Aug 2005
CORNELL UNIV ITHACA NY
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Retinoic acid RA regulates the proliferation of a wide variety of cell types through the action of retinoic acid receptors. Phytanic acid PA and docosahexaenoic acid DHA are diet-derived fatty acids that bind to rexinoid X receptors RXR. Therefore, we hypothesized that inhibitory effects on cell proliferation may be enhanced by the addition of PA and DHA to RA- treated cells. We demonstrate that 1 the combination of PA or DHA with RA resulted in enhanced growth arrest of estrogen receptor positive human breast cancer HBC cells 2 PA and DHA induced growth arrest of estrogen receptor negative HBC cells 3 synthetic RXR agonists induced growth inhibitory effects similar to PA and DHA in HBC cells and 4 PA enhanced RA-induced expression of ribo mRNA in HBO cells and in murine embryonic stem cells. Our data indicate that PA and DHA may be useful adjuvant agents when retinoids are used to inhibit cell proliferation andor to induce cell differentiation. Deciphering the effects of diet-derived RXR agonists may lead to new therapeutic and experimental uses of these agents in combination with retinoids.
- Anatomy and Physiology
- Medicine and Medical Research