MAPK信号通路相关信号转导分子在人乳腺癌细胞系中的表达及活化水平

Expression and activation of MAPK pathway signaling molecules in human breast cancer cell lines

目的 :检测化疗药物环磷酰胺及表阿霉素对 4种乳腺癌细胞增殖的抑制作用 ,以及对细胞外信号调节激酶 (ERK1/2 )及其上游激酶 (MEK1/2 )蛋白表达及活化水平的影响。方法 :按常规方法培养细胞及制备蛋白电泳样品。应用Westernblot检测培养的正常乳腺上皮细胞系MCF 10及MCF 7、T4 7D、Bcap 37、SK BR 3乳腺癌细胞系中 ,ERK1/2和MEK1/2的表达及活化 (磷酸化 )水平 ,以及这两种药物对ERK1/2和MEK1/2的表达及活化的影响。用MTT比色法检测这两种化疗药物对乳腺癌细胞增殖的抑制作用。结果 :与对照MCF 10细胞相比较 ,4种乳腺癌细胞系中 ,MEK1/2、ERK1/2蛋白的表达及活化水平均明显增高 ;两种化疗药物均可抑制乳腺癌细胞的增殖。这两种药物处理的乳腺癌细胞中 ,MEK1/2、ERK1/2蛋白的表达及其活化水平明显低于未处理组。结论 :MEK、ERK蛋白的过度表达及活化 ,可能在人乳腺癌的发生、发展中起重要作用。这两种化疗药物可能是通过抑制MEK。

AIM: To detect the expression and status of extracellular regulatory kinase 1 and 2 (ERK1/2) and its upstream kinase MEK1/2 proteins in four breast cancer cell lines MCF 7, Bcap 37, SK BR 3 and T47D and study the effects of cyclophosphamide and epirubicin on the growth of the cell lines and on the expression and status of the signaling molecules. METHODS: Western blot was used to examine the expression and status of MEK1/2 and ERK1/2 proteins in these cells and the effects of these two drugs on them. The effects of the two drugs on the proliferation of these breast cancer cell lines were detected by MTT colorimetry. RESULTS: The levels of expression and phosphorylation of MEK1/2 and ERK1/2 proteins in four breast cancer cell lines increased notably as compared with those in MCF 10 cells. Both drugs could inhibit the proliferation of breast cancer cells. And the levels of expression and phosphorylation of MEK1/2 and ERK1/2 proteins in breast cancer cell lines treated with the drugs were markedly lower than those in untreated breast cancer cells. CONCLUSION: Overexpression and phosphorylation of MEK and ERK may play an important role in the generation and development of human breast cancer. The inhibitory effect of cyclophosphamide and epirubicin on proliferation of the breast cancer cells may be by means of ihibiting expression and phosphorylation of MEK and ERK.