Valladares Macarena, Plaza-Parrochia Francisca, Lépez Macarena, López Daniela, Gabler Fernando, Gayan Patricio, Selman Alberto, Vega Margarita, Romero Carmen
Laboratory of Endocrinology and Reproduction Biology, Clinical Hospital, University of Chile, Santiago, Chile.
Laboratorio de Bionanotecnología, Universidad Bernardo O'Higgins, Santiago, Chile.
Histol Histopathol. 2017 Nov;32(11):1187-1196. doi: 10.14670/HH-11-874. Epub 2017 Jan 24.
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.
To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC).
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.
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).
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.
卵巢癌呈现出高血管生成（新血管形成），这受促血管生成因子调控，主要是血管内皮生长因子（VEGF）和神经生长因子（NGF）。已有报道称内源性雌激素水平与患卵巢癌风险增加之间存在关联。雌激素的作用通过与其特异性受体（ERα和ERβ）结合来介导，ERα/ERβ比值改变可能构成卵巢癌发生发展的一个标志物。
确定雌二醇通过ERα对上皮性卵巢癌（EOC）中NGF和VEGF表达的影响。
在高分化、中分化和低分化的EOC样本（EOC-I、EOC-II、EOC-III）中评估磷酸化雌激素受体α（pERα）的水平。此外，用NGF（0、10和100 ng/ml）刺激卵巢癌外植体，并检测ERα、ERβ和pERα水平。最后，用雌二醇刺激人卵巢表面上皮（HOSE）和上皮性卵巢癌（A2780）细胞系，评估NGF和VEGF蛋白水平。
在组织中，检测到ERs，与EOC-I相比，EOC-III样本中的pERα水平显著升高（p<0.05）。此外，用NGF处理的卵巢外植体pERα水平升高，而总ERα和ERβ水平不变。用雌二醇刺激的细胞系显示NGF和VEGF蛋白水平升高（p<0.05）。
雌二醇可能通过激活ERα对EOC中促血管生成因子如NGF和VEGF的表达产生积极影响；在卵巢上皮细胞中产生由NGF增加pERα水平诱导的正反馈循环。
