title: Tristetraprolin represses estrogen receptor α transactivation in breast cancer cells.
abstract: Estrogen receptor α (ERα) mediates the effects of 17β-estradiol (E2) in normal mammary gland, and it is a key participant in breast cancer tumor development. ERα transactivation activity is mediated by the synergistic interaction of two domains designated AF1 and AF2. The function of AF2 is to recruit coactivator and corepressor proteins that allow ERα to oscillate between the roles of transcriptional activator and repressor. In contrast, the mechanism responsible for AF-1 transcriptional activity is not completely understood. In this study, we identified tristetraproline (TTP) as a novel ERα-associated protein. TTP expression in MCF7 cells repressed ERα transactivation and reduced MCF7 cell proliferation and the ability of the cells to form tumors in a mouse model. We show that TTP transcriptional activity is mediated through its recruitment to the promoter region of ERα target genes and its interaction with histone deacetylases, in particular with HDAC1. TTP expression attenuates the coactivating activity of SRC-1, suggesting that exchange between TTP and other coactivators may play an important role in fine-tuning ERα transactivation. These results indicate that TTP acts as a bona fide ERα corepressor and suggest that this protein may be a contributing factor in the development of E2-dependent tumors in breast cancer.
authors.affiliation: From the Programa de Investigación de Cáncer de Mama and Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D. F. 04510, Mexico.
authors.forename: Tonatiuh
authors.initials: T
authors.lastname: Barrios-García
authors.affiliation: From the Programa de Investigación de Cáncer de Mama and Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D. F. 04510, Mexico.
authors.forename: Angeles
authors.initials: A
authors.lastname: Tecalco-Cruz
authors.affiliation: From the Programa de Investigación de Cáncer de Mama and Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D. F. 04510, Mexico.
authors.forename: Vania
authors.initials: V
authors.lastname: Gómez-Romero
authors.affiliation: From the Programa de Investigación de Cáncer de Mama and Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D. F. 04510, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reyes-Carmona
authors.affiliation: From the Programa de Investigación de Cáncer de Mama and Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D. F. 04510, Mexico.
authors.forename: Iván
authors.initials: I
authors.lastname: Meneses-Morales
authors.affiliation: From the Programa de Investigación de Cáncer de Mama and Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D. F. 04510, Mexico leon@biomedicas.unam.mx.
authors.forename: Alfonso
authors.initials: A
authors.lastname: León-Del-Río
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D056970:Co-Repressor Proteins / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014158:Transcription, Genetic / Q000502:physiology; D051816:Tristetraprolin / Q000378:metabolism*
chemical_list: D056970:Co-Repressor Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D004958:Estradiol; D006655:Histone Deacetylases
keywords: Corepressor Transcription; Estrogen Receptor; Gene Regulation; Hormone Receptors; Nuclear Receptors; Tristetraprolin
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