title: Estradiol increases cell growth in human astrocytoma cell lines through ERα activation and its interaction with SRC-1 and SRC-3 coactivators.
abstract: Estradiol (E2) regulates several cellular functions through the interaction with estrogen receptor subtypes, ERα and ERβ, which present different functional and regulation properties. ER subtypes have been identified in human astrocytomas, the most common and aggressive primary brain tumors. We studied the role of ER subtypes in cell growth of two human astrocytoma cell lines derived from tumors of different evolution grades: U373 and D54 (grades III and IV, respectively). E2 significantly increased the number of cells in both lines and the co-administration with an ER antagonist (ICI 182, 780) significantly blocked E2 effects. ERα was the predominant subtype in both cell lines. E2 and ICI 182, 780 down-regulated ERα expression. The number of U373 and D54 cells significantly increased after PPT (ERα agonist) treatment but not after DPN (ERβ agonist) one. To determine the role of SRC-1 and SRC-3 coactivators in ERα induced cell growth, we silenced them with RNA interference. Coactivator silencing blocked the increase in cell number induced by PPT. The content of proteins involved in proliferation and metastasis was also determined after PPT treatment. Western blot analysis showed that in U373 cells the content of PR isoforms (PR-A and PR-B), EGFR, VEGF and cyclin D1 increased after PPT treatment while in D54 cells only the content of EGFR was increased. Our results demonstrate that E2 induces cell growth of human astrocytoma cell lines through ERα and its interaction with SRC-1 and SRC-3 and also suggest differential roles of ERα on cell growth depending on astrocytoma grade.
authors.affiliation: Facultad de Química, Departamento de Biología, Universidad Nacional Autóma de México, Ciudad Universitaria, Coyoacán, Mexico.
authors.forename: Aliesha
authors.initials: A
authors.lastname: González-Arenas
authors.forename: Valeria
authors.initials: V
authors.lastname: Hansberg-Pastor
authors.forename: Olivia Tania
authors.initials: OT
authors.lastname: Hernández-Hernández
authors.forename: Tania Karina
authors.initials: TK
authors.lastname: González-García
authors.forename: Joshua
authors.initials: J
authors.lastname: Henderson-Villalpando
authors.forename: Diana
authors.initials: D
authors.lastname: Lemus-Hernández
authors.forename: Aglaé
authors.initials: A
authors.lastname: Cruz-Barrios
authors.forename: Mariana
authors.initials: M
authors.lastname: Rivas-Suárez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Camacho-Arroyo
mesh_terms: D001254:Astrocytoma / Q000473:pathology / Q000503:physiopathology*; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism*; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D020033:Protein Isoforms; D011980:Receptors, Progesterone; D019938:Cyclin D1; D004958:Estradiol; C538866:NCOA3 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor