title: Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.
abstract: BACKGROUND
  Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression.
  
  
  OBJECTIVE
  To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC).
  
  
  METHODS
  Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated.
  
  
  RESULTS
  In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05).
  
  
  CONCLUSIONS
  Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.
authors.affiliation: Laboratory of Endocrinology and Reproduction Biology, Clinical Hospital, University of Chile, Santiago, Chile.|Laboratorio de Bionanotecnología, Universidad Bernardo O'Higgins, Santiago, Chile.
authors.forename: Macarena
authors.initials: M
authors.lastname: Valladares
authors.affiliation: Laboratory of Endocrinology and Reproduction Biology, Clinical Hospital, University of Chile, Santiago, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Plaza-Parrochia
authors.affiliation: Laboratory of Endocrinology and Reproduction Biology, Clinical Hospital, University of Chile, Santiago, Chile.
authors.forename: Macarena
authors.initials: M
authors.lastname: Lépez
authors.affiliation: Laboratory of Endocrinology and Reproduction Biology, Clinical Hospital, University of Chile, Santiago, Chile.
authors.forename: Daniela
authors.initials: D
authors.lastname: López
authors.affiliation: Department of Pathology, School of Medicine, San Borja Arriarán Clinical Hospital, University of Chile, Santiago, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gabler
authors.affiliation: National Institute of Cancer, Santiago, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Gayan
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Clinical Hospital, University of Chile, Santiago, Chile.
authors.forename: Alberto
authors.initials: A
authors.lastname: Selman
authors.affiliation: Laboratory of Endocrinology and Reproduction Biology, Clinical Hospital, University of Chile, Santiago, Chile.|Department of Obstetrics and Gynecology, School of Medicine, Clinical Hospital, University of Chile, Santiago, Chile.
authors.forename: Margarita
authors.initials: M
authors.lastname: Vega
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Clinical Hospital, University of Chile, Santiago, Chile.|Laboratory of Endocrinology and Reproduction Biology, Clinical Hospital, University of Chile, Santiago, Chile. cromero@hcuch.cl.
authors.forename: Carmen
authors.initials: C
authors.lastname: Romero
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology*; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C502240:NGF protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol; D020932:Nerve Growth Factor