雌激素受体
雌激素
癌症研究
基因敲除
雌激素受体α
MAPK/ERK通路
表皮生长因子受体
雌激素受体
信号转导
细胞周期蛋白D1
细胞生长
下调和上调
生物
磷酸化
内科学
内分泌学
细胞
受体
细胞生物学
细胞周期
细胞培养
癌症
医学
乳腺癌
基因
生物化学
遗传学
作者
Chao Qu,Cui Wang,Hongyan Li,Ying Li,Chao Han,Xiaofeng Tao,Xin Guan,Yejun Zhang,Meng Chen,Jing Liu,Wei Zou
摘要
Abstract Glioblastoma (GBM) is a deadly and common primary brain tumor. Poor prognosis is linked to high proliferation and cell heterogeneity. Sex differences may play a role in patient outcome. Previous studies showed that ER‐α36, a variant of the estrogen receptor (ER), mediated non‐genomic estrogen signaling and is highly expressed in many ER‐negative malignant tumors. ER‐α36 also associates with epidermal growth factor receptor (EGFR). The primary purpose of this study is to investigate the cross talk between ER‐α36 and EGFR in estrogen‐mediated GBM cell proliferation. Here, we showed that ER‐α36 was highly expressed and confirmed that ER‐α36 co‐labels with EGFR in human GBM samples using immunohistochemical techniques. We also investigated the mechanisms of estrogen‐induced proliferation in ER‐α‐negative cell lines. We found that GBM cells showed varying responsive to mitogenic estrogen signaling which correlated with ER‐α36 expression, and knockdown of ER‐α36 diminished the response. Exposure to estrogen also caused upregulation of cyclin protein expression in vitro. We also found that low concentration of estrogen promoted SRC‐Y‐416 and inhibited SRC‐Y‐527 phosphorylation, corresponding with activated SRC signaling. Inhibiting SRC or EGFR abolished estrogen‐induced mitogenic signaling, including cyclin expression and MAPK phosphorylation. Cumulatively, our results demonstrate that ER‐α36 promotes non‐genomic estrogen signaling via the EGFR/SRC/MAPK pathway in GBM. This may be important for the treatment of ER‐α‐negative GBMs that retain high level of ER‐α36, since estrogen may be a viable therapeutic target for these patients.
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