The objective of this application is to determine the mechanism by which retinoids inhibit the growth of ovarian cancer cells. It is proposed to: (1) Elucidate the important molecular events in the pathway by which AHPN induces apoptosis in ovarian carcinoma cells. More specifically, the role of the RARs and RXRs in AHPN induced apoptosis of ovarian carcinoma cells, and the importance and function of ligand binding to RAR-g in mediating the induction of apoptosis by AHPN, will be determined; and (2) Investigate the mechanism by which retinoid antagonism of AP-1 activity mediates the retinoid-dependent suppression of ovarian carcinoma cell growth. More specifically, RA mediated changes in expression and phosphorylation status of AP-1 components, the role of co- activators such as CBP and p300, and the use of RAR-b isoforms to map the sequences of RARs that are essential for this activity, will be examined.
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