GPR30-EGFR信号通路在双酚A促乳腺癌细胞增殖中的作用

目的:探讨GPR30-EGFR信号传导通路在双酚A促乳腺癌MCF-7细胞增殖中的作用,为研究双酚A诱导乳腺癌的确切机制提供依据。方法:采用Western blot检测双酚A处理乳腺癌MCF-7细胞24 h和48 h后GPR30-EGFR的表达情况,采用MTT法检测AG1478抑制EGFR后双酚A对乳腺癌细胞增殖的影响。结果:EGFR在1μM双酚A作用48 h后其诱导表达最明显(P<0.05);GPR30在双酚A作用48 h后表达下调明显(P<0.05)。通过EGFR的高选择性抑制剂AG1478对乳腺癌细胞中的EGFR进行阻断,当AG1478和双酚A协同作用时,乳腺癌MCF-7细胞的增殖相对于双酚A单独作用组无明显区别(P>0.05)。结论:在双酚A所诱导的乳腺癌MCF-7细胞的增殖作用中,EGFR被有效地激活,GPR30蛋白在与双酚A作用后表达有所减弱;EGFR不是双酚A促细胞增殖的必经通路,双酚A可能通过其他通路发挥促细胞增殖作用。

Effect of Bisphenol A on the GPR30-EGFR pathway in breast cancer cell

Objective:To explore the effect of GPR30-EGFR signaling pathway in bisphenol A(BPA) induced proliferation effect on MCF-7 cell and provide the basis for the mechanism of how BPA induces breast cancers. Methods:Gene expressions of GPR30,EGFR were assayed on the translational level by Western blot after 1 μmol/L BPA treatment for 24 and 48 h.MTT cytotoxcity assay was applied to explore the mechanism of BPA on breast cancer cell proliferation through inhibiting EGFR with its inhibitor AG1478. Results:The expression of EGFR was up-regulated remarkably after 1 μmol/L BPA treatment for 48 h(P<0.05).The expression of GPR30 was down regulated potently after BPA treatment for 48 h(P<0.05).The stimulation of proliferation in MCF-7 cell by the combined treatment with BPA and AG1478 for 48 h resulted in similar effects with the treatment of BPA alone(P>0.05). Conclusion:EGFR is effectively activated in the BPA-induced proliferation of MCF-7 cell with the evidence of strong induction of targeting protein by the continuous treatment of BPA.However,the expression of GPR30 decreases obviously after binding with BPA.EGFR is not a necessary way in the BPA-induced proliferation effect,BPA can promote cell's proliferation through other pathways