title: Progesterone receptor and SRC-1 participate in the regulation of VEGF, EGFR and Cyclin D1 expression in human astrocytoma cell lines.
abstract: Astrocytomas are the most common primary brain tumors in humans. It has been reported that vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), cyclin D1 and progesterone receptor (PR) expression levels are elevated in patients with high-grade astrocytomas. Progesterone (P) regulates astrocytomas growth through its interaction with PR, which recruits coregulatory proteins such as steroid receptor coactivator-1 (SRC-1) that are required for efficient transcriptional activation. The regulation of VEGF, EGFR and cyclin D1 expression by P in human astrocytoma cells is not known. We studied the role of PR and SRC-1 in the expression of VEGF, EGFR and cyclin D1 mediated by P in human astrocytoma cell lines grade III (U373) and IV (D54). P significantly increased VEGF and EGFR mRNA expression after 12h of treatment in D54 cells that was reflected at protein level 24h after treatment. This effect was blocked by the PR antagonist, RU 486. In U373 cells cyclin D1 mRNA and protein expression was induced by P after 6 and 8h of treatment, respectively, and this effect was blocked with RU 486. Transfection with short hairpin RNA targeting coactivator SRC-1 significantly reduced VEGF expression after 24h of treatment. Collectively, our results indicate that P regulates VEGF and EGFR expression in D54 cells and cyclin D1 expression in U373 through PR, and that SRC-1 participates in the regulation of VEGF expression.
authors.affiliation: Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Olivia Tania
authors.initials: OT
authors.lastname: Hernández-Hernández
authors.forename: Tania Karina
authors.initials: TK
authors.lastname: González-García
authors.forename: Ignacio
authors.initials: I
authors.lastname: Camacho-Arroyo
mesh_terms: D001254:Astrocytoma; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; D006727:Hormone Antagonists; D011372:Progestins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; D015735:Mifepristone; D011374:Progesterone; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; C512478:EGFR protein, human; D066246:ErbB Receptors