细胞外信号调节激酶及其上游激酶在人乳腺癌发生发展中的意义

目的　研究人乳腺癌组织、良性肿瘤以及瘤旁乳腺组织中细胞外信号调节激酶 (ERK1、ERK2 )及其上游激酶 (MEK1、MEK2 )的表达 ,以及术前化疗对MEK1、MEK2、ERK1、ERK2蛋白表达的影响。　方法　应用蛋白质印迹法检测 5 6例患者乳腺癌组织、8例乳腺良性肿瘤以及相应瘤旁组织中MEK1、MEK2及ERK1、ERK2蛋白的表达情况 ,其中 16例患者术前接受环磷酰胺 ,表阿霉素加 5 氟脲嘧啶或泰素加表阿霉素方案化疗。应用免疫组织化学方法检测乳腺癌组织及癌旁组织中MEK1、MEK2及ERK1、ERK2蛋白的表达。　结果　 4 0例未行术前化疗的乳腺癌组织中MEK2、ERK1、ERK2蛋白表达水平高于癌旁组织 ,分别为癌旁组织的 4 76、1 4 8和 2 0 9倍 (t值分别为 7 2 4 4 ,5 95 9,3 735 ,P <0 0 1) ;MEK1水平低于相应癌旁组织 (t=2 2 0 6 ,P <0 0 5 ) ;未行术前化疗的乳腺癌组织中MEK2、ERK1、ERK2蛋白表达水平高于乳腺良性肿瘤 (t值分别为 2 932 ,2 0 82 ,2 0 2 1,P <0 0 5 ) ;MEK1水平低于良性肿瘤 (t=2 0 75 ,P <0 0 5 ) ;雌激素受体阴性的乳腺癌中MEK2蛋白表达水平高于雌激素受体阳性的肿瘤 (t=2 4 0 ,P <0 0 5 ) ,MEK1蛋白表达水平低于雌激素受体阳性的肿瘤 (t =2 5 8,P <0 0 1) ;术前化疗的乳腺癌组织中MEK2蛋白表达

Significance of MEK-ERK cascade in the development of human breast carcinoma

Objective To investigate the MEK and ERK expression and their relationship with clinicopathological parameters in human breast carcinoma, and the effect of preoperative chemotherapy on MEK and ERK protein expression. Methods Samples were obtained from 56 patients with breast carcinoma and 8 patients with benign tumors. Sixteen of the 56 patients received preoperative chemotherapy. Western blot and immunohistochemistry were used to measure the expression of MEK1, MEK2 and ERK1, ERK2 protein. Results MEK2 and ERK1, ERK2 protein levels were increased in breast carcinoma tissue compared with those in adjacent normal tissues ( t =7 244?5 959?3 735, P <0 01) and benign tumors ( t =2 206, P <0 05). The levels of MEK1 were decreased. The expression of MEK2 protein in ER negative patients was higher than that in ER positive ones. MEK2 protein levels were lower in patients who received preoperative chemotherapy than in those who did not. Conclusion Overexpression of MEK ERK may play an important role in the development of human breast carcinoma. MEK and ERK protein expressions are inhibited by preoperative chemotherapy.