GPR30-EGFR信号通路在双酚A促乳腺癌细胞增殖中的作用

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

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。

Objective： To explore the effect of GPR30 - EGFR signaling pathway in bispheuol 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 Ixmol/L BPA treatment for 24 and 48 h. MTT cytotoxcity assay was ap- plied 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 txmol/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 activa- ted in the BPA - induced proliferation of MCF - 7 cell with the evidence of strong induction of targeting pl＂otein 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 pro- liferation effect. BPA can oromote cell~ proliferation through other pathways