title: CBP/p300 induction is required for retinoic acid sensitivity in human mammary cells.
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.
authors.affiliation: Division of Medical Oncology and Transplantation, Duke University Medical Center, Box 2628, Durham, NC 27710, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Dietze
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Troch
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Bowie
authors.forename: Lisa
authors.initials: L
authors.lastname: Yee
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Bean
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Seewaldt
mesh_terms: D001940:Breast / Q000166:cytology / Q000378:metabolism*; D050882:CREB-Binding Protein; D002453:Cell Cycle / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D015534:Trans-Activators; C082925:retinoic acid receptor beta; D014212:Tretinoin; D050882:CREB-Binding Protein; C494363:CREBBP protein, human