title: Novel role for PINX1 as a coregulator of nuclear hormone receptors.
abstract: Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process influenced by coactivator and corepressor proteins. This work shows that Pin2 interacting protein 1 (PINX1) interacts with the N-terminal domain of ERα and functions as a corepressor of ERα. Furthermore, it represses both AF-1 and AF-2 transcriptional activities. Chromatin immunoprecipitation assays verified that the interaction between ERα and PINX1 occurs on E2 regulated promoters and enhanced expression of PINX1 deregulates the expression of a number of genes that have a role in cell growth and proliferation in breast cancer. PINX1 overexpression decreases estrogen mediated proliferation of breast cancer cell lines, while its depletion shows the opposite effect. Taken together, these data show a novel molecular mechanism for PINX1 as an attenuator of estrogen receptor activity in breast cancer cell lines, furthering its role as a tumor suppressor gene in breast cancer.
authors.affiliation: Departamento de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080, Mexico D.F., Mexico; Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de Mexico. D.F., Mexico.
authors.forename: Maria Yamilet
authors.initials: MY
authors.lastname: Noriega-Reyes
authors.affiliation: Departamento de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080, Mexico D.F., Mexico; Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de Mexico. D.F., Mexico.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Rivas-Torres
authors.affiliation: Departamento de Investigación Clínica, Instituto Nacional de Cancerología, Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080, Mexico D.F., Mexico.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Oñate-Ocaña
authors.affiliation: Institut de Biología Molecular de Barcelona (IBMB-CSIC) Parc Científic de Barcelona, Barcelona, Cataluña, España.
authors.forename: Albert Jordan
authors.initials: AJ
authors.lastname: Vallés
authors.affiliation: Departamento de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080, Mexico D.F., Mexico.
authors.forename: Noemi
authors.initials: N
authors.lastname: Baranda-Avila
authors.affiliation: Departamento de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080, Mexico D.F., Mexico. Electronic address: langleyemx@gmail.com.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Langley
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019556:COS Cells; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D047628:Estrogen Receptor alpha; C440808:PINX1 protein, human; D025521:Tumor Suppressor Proteins
keywords: Breast cancer; Corepressors and transcriptional regulation; Estrogen receptor; PINX1