CCAAT/enhancer binding protein β negatively regulates progesterone receptor expression in human glioblastoma cells.
Many progesterone (P4) actions are mediated by its intracellular receptor (PR), which has two isoforms (PR-A and PR-B) differentially transcribed from separate promoters of a single gene. In glioblastomas, the most frequent and aggressive brain tumors, PR-B is the predominant isoform. In an in silico analysis we showed putative CCAAT/Enhancer Binding Protein (C/EBP) binding sites at PR-B promoter. We evaluated the role of C/EBPβ in PR-B expression regulation in glioblastoma cell lines, which expressed different ratios of PR and C/EBPβ isoforms (LAP1, LAP2, and LIP). ChIP assays showed a significant basal binding of C/EBPβ, specific protein 1 (Sp1) and estrogen receptor alpha (ERα) to PR-B promoter. C/EBPβ knockdown increased PR-B expression and treatment with estradiol (E2) reduced C/EBPβ binding to the promoter and up-regulated PR-B expression. P4 induced genes were differently regulated when CEBP/β was silenced. These data show that C/EBPβ negatively regulates PR-B expression in glioblastoma cells.
Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México (UNAM), Mexico.
Valeria
V
Hansberg-Pastor
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, Mexico.
Aliesha
A
González-Arenas
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, UNAM, Ciudad de México, Mexico. Electronic address: camachoarroyo@gmail.com.
Ignacio
I
Camacho-Arroyo
D001665:Binding Sites / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003198:Computer Simulation; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D011374:Progesterone / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D020033:Protein Isoforms; D011980:Receptors, Progesterone; D016329:Sp1 Transcription Factor; D011374:Progesterone; D004958:Estradiol
CCAAT-enhancer binding protein beta; Cancer; Gene expression; Glioblastoma; Progesterone receptor; Repressor