# D312 All-trans-retinoic acid but not tamoxifen induce CBP and p300 expression: A rational for retinoid-chemoprevention. Victoria Seewaldt, Michelle Bowie, Michelle Troch, Josh Heffner, Gregory Bean and Eric Dietze, Duke University, Durham, NC. CBP and p300 are coactivators of estrogen- and retinoid-signaling, regulate proliferation and apoptosis, and are hypothesized to play an important role in transcription-coupled DNA repair. The transcriptional regulation of CBP and p300 themselves is poorly understood. All-trans-retinoic acid but not tamoxifen induced CPB/p300 mRNA and protein expression in normal human mammary epithelial cells (HMECs). To assess whether CBP and p300 are regulated by retinoic acid receptors (RARs) two systems were tested: 1) ATRA-resistant MCF-7 breast cancer cells were transduced with a functional RAR-beta2 and 2) human mammary epithelial cells (HMECs) were transduced with the dominant negative RAR, RAR-alpha403. Expression of RAR-beta2 in MCF-7 cells resulted in increased sensitivity to ATRA and increased CBP/p300 protein and mRNA levels upon ATRA treatment. Inhibition of RAR function in HMECs resulted in resistance to ATRA, decreased CBP and p300 protein and mRNA levels, and loss of CBP and p300 induction upon ATRA treatment. Suppression of CBP or p300 in HMECs resulted in a loss of sensitivity to ATRA. Loss of ATRA-mediated growth inhibition and decreased transactivation of a RARE-driven CAT reporter were observed. CBP and p300 are normally present in limiting amounts and are recruited during ATRA mediated transcriptional regulation, their regulation by ATRA and RARs may be an important element in transcriptional control of ATRA regulated gene expression in HMECs. CBP and p300 are required for growth regulation and apoptosis and can be downregulated in cancer. Therefore, a means of upregulating CBP and p300 by retinoids may be an useful adjunct in the prevention of breast cancer. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.