Literature DB >> 12646247

CBP/p300 induction is required for retinoic acid sensitivity in human mammary cells.

Eric C Dietze1, Michelle M Troch, Michelle L Bowie, Lisa Yee, Gregory R Bean, Victoria L Seewaldt.   

Abstract

The coactivators CBP and p300 are recruited by retinoic acid receptors (RARs) during retinoid mediated transcriptional regulation. To assess the role of CBP/p300 in all-trans-retinoic acid (ATRA)-mediated growth arrest in mammary epithelial cells, two systems were tested: (1) ATRA resistant MCF-7 cells were transduced with a functional RAR-beta 2; (2) normal human mammary epithelial cells (HMECs) were transduced with a pan-RAR dominant negative, RAR-alpha 403. Expression of RAR-beta 2 in MCF-7 cells resulted in increased sensitivity to ATRA-induced growth arrest and correlated with induction of CBP/p300 mRNA and protein. Inhibition of RAR function in HMECs resulted in resistance to ATRA-induced growth arrest and loss of CBP/p300 induction. Antisense suppression of CBP/p300 in HMECs resulted in decreased retinoic acid response element reporter trans-activation and decreased ATRA-mediated growth arrest. Thus, in human mammary epithelial cells, CBP/p300 were both modulated by an ATRA signaling pathway and were required for a normal response to ATRA.

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Year:  2003        PMID: 12646247     DOI: 10.1016/s0006-291x(03)00266-3

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


  13 in total

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