乳腺癌中雌激素诱导的细胞增殖与有丝分裂素激活蛋白激酶活性的关系

目的探讨雌二醇与有丝分裂素激活蛋白激酶(MAPK)信号通路的关系以及MAPK在乳腺癌细胞系中的表达情况。方法分别用上皮生长因子(EGF)和不同浓度的雌二醇诱导人类乳腺癌细胞系MCF-7细胞,诱导不同时间后用Western blot方法检测磷酸化ERK1／2的表达;用抗雌激素物质ICI182780和MAPK抑制剂PD98059作用于雌二醇诱导的MCF-7细胞,检测磷酸化ERK1／2的表达;用流式细胞仪检测雌二醇对MCF-7细胞周期的影响。结果MAPK信号通路的诱导剂EGF可以明显诱导磷酸化MAPK的表达;雌二醇也可以诱导磷酸化MAPK的表达。PD98059可以完全抑制雌二醇诱导的磷酸化ERK1／2水平,而ICI182780只能减少雌二醇诱导的磷酸化ERK1／2的表达。随着作用时间的延长,雌二醇可以使MCF-7细胞G2／M期的细胞数增加。结论雌二醇、雌激素受体与MAPK信号途径关系较为密切,MAPK是乳腺癌中重要的调节信号。

Relationship between estradiol and the mitogenic activated protein kinase signal transduction pathway

Objective To discuss the relationship between estradiol and the mitogenic activated protein kinase signal transduction pathway and the expression of the MAPK in the MCF-7 breast cancer cell-line. Methods Epithelial growth factor (EGF) and different concentration of estradiol to induce the expression of phosphospecific ERK1/2 (pERK1/2) in MCF-7 cell line was used and the expression of pERK1/2 with western-bloting was detected. Then antiestrogen ICI 182780 and MAPK inhibitor PD98059 to inhibit the expression of pERK1/2 was used. The cell cycle of MCF-7 was detected by FACS. Results EGF could significantly induce the expression of pERK1/2. Estradiol could also induce the expression of pERK1/2, but the intensity was less than the induction of EGF. The percentage of cells in the G 2/M cell cycle after estradiol induction increased (18.38%) compared to the control group (10.52%) ( P <0.05). Conclusions MAPK is an important regulatory signal in breast cancer. Its measurement in breast cancer tissues provides information about the degree of activation of various growth factor pathways. This molecule may also provide a molecular target for compounds designed to block cell proliferation.