Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

Abstract

INTRODUCTION:

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).

METHODOLOGY:

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: Macarena Valladares, Francisca Plaza-Parrochia, Macarena Lépez, Daniela López, Fernando Gabler, Patricio Gayan, Alberto Selman, Margarita Vega, Carmen Romero
• Journal: Histology and histopathology (Histol Histopathol) Vol. 32 Issue 11 Pg. 1187-1196 (Nov 2017) ISSN: 1699-5848 [Electronic] Spain
• PMID: 28116735 (Publication Type: Journal Article)

Chemical References

• ESR1 protein, human
• Estrogen Receptor alpha
• NGF protein, human
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Estradiol
• Nerve Growth Factor

Topics

• Carcinoma, Ovarian Epithelial
• Estradiol (pharmacology)
• Estrogen Receptor alpha (biosynthesis)
• Female
• Humans
• Neoplasms, Glandular and Epithelial (metabolism, pathology)
• Nerve Growth Factor (biosynthesis, drug effects)
• Ovarian Neoplasms (metabolism, pathology)
• Vascular Endothelial Growth Factor A (biosynthesis)