title: Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer.
abstract: Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells.
authors.affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom.
authors.forename: Caryn S
authors.initials: CS
authors.lastname: Ross-Innes
authors.forename: Rory
authors.initials: R
authors.lastname: Stark
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Holmes
authors.forename: Dominic
authors.initials: D
authors.lastname: Schmidt
authors.forename: Christiana
authors.initials: C
authors.lastname: Spyrou
authors.forename: Roslin
authors.initials: R
authors.lastname: Russell
authors.forename: Charlie E
authors.initials: CE
authors.lastname: Massie
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Vowler
authors.forename: Matthew
authors.initials: M
authors.lastname: Eldridge
authors.forename: Jason S
authors.initials: JS
authors.lastname: Carroll
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*
chemical_list: D004967:Estrogens; D008024:Ligands; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D004247:DNA