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雌激素激活GPR30/ERK通路促进三阴性乳腺癌MDA-MB-468细胞迁移及侵袭

, PP. 2077-2082

Keywords: 雌激素,GPR/ERK通路,三阴性乳腺癌,细胞迁移及侵袭

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Abstract:

目的探讨雌激素/GPR30/ERK信号通路的激活对三阴性乳腺癌(triple-negativebreastcancer,TNBC)MDA-MB-468细胞迁移及侵袭的影响。方法免疫荧光及Westernblot检测MDA-MB-468细胞中雌激素受体GPR30的蛋白表达量及细胞内定位,Westernblot检测药物处理后细胞中磷酸化细胞外信号调节激酶(phospho-extracellularregulatekinase,p-ERK)的蛋白表达变化,细胞划痕实验及Transwell小室实验分别检测细胞的迁移及侵袭能力的改变。结果雌激素受体GPR30在TNBC细胞系MDA-MB-468中高表达,且主要位于细胞胞浆部位。17-β雌二醇(E2)和GPR30特异性激动剂(G1)可以显著活化细胞中GPR30/ERK信号通路(P<0.05),上调p-ERK蛋白水平,其相对表达量分别是空白对照组的(2.07±0.11)倍和(1.98±0.06)倍。E2及G1药物处理后的细胞迁移能力得到显著提高(P<0.05),24h后迁移入划痕区域的相对细胞数分别为空白对照组的(2.10±0.20)倍和(2.14±0.34)倍。细胞侵袭实验也可得到类似结果。GPR30特异性拮抗剂(G15)以及ERK特异性抑制剂(U0126)均可显著抑制E2和G1引发的以上改变(P<0.05)。结论雌激素通过活化TNBC细胞MDA-MB-468中GPR30/ERK信号通路,促进细胞迁移及侵袭的恶性潜能。靶向雌激素/GPR30/ERK通路可能成为TNBC的有效治疗手段。

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