Expression of mitogen-activated protein kinase and its upstream regulated signal in human hepatocellular carcinoma

目的探讨有丝分裂原蛋白激酶(MAPK)通路在调控细胞的增殖和凋亡过程中所起到的作用.方法手术切除16份肝癌及癌旁组织标本,Western印迹检测ERK1、ERK2、JNK1、p38和MEK1、MEK2的蛋白含量.结果在本组的16例患者中,每例患者肝癌组织中的ERK1、ERK2、JNK1、p38蛋白表达显著高于癌旁组织,ERK1积分光密度值(Integral optic density IOD)在肝癌和癌旁组织中分别为300±98和98±48,差异有显著意义(P＜0.01).ERK2的IOD值在肝癌和癌旁组织中分别为587±83和232±96,差异有显著意义(P＜0.01);p38的IOD值在肝癌和癌旁组织中分别为270±85和107±88,差异有显著意义(P＜0.01);肝癌组织中的JNK1蛋白表达显著低于癌旁组织;JNK1的IOD值在肝癌和癌旁组织中分别为111±93和292±109,差异有显著意义(P＜0.01);MEK1、MEK2蛋白表达显著高于癌旁组织,MEK1的IOD值在肝癌和癌旁组织中分别为1418±244和806±90,差异有显著意义(P＜0.01),MEK2的IOD值在肝癌和癌旁组织中分别为1041±122和468±40,差异有显著意义(P＜0.05).结论在肝癌组织中细胞分裂增殖的信号传导通路ERK1、ERK2、MEK1、MEK2激酶处于高表达,JNK1激酶在肝癌组织中处于低表达,它们的失衡导致肝癌细胞生长失控和无限增殖的重要原因之一.JNK1和p38在肝癌组织中可能存在不同的激活途径.Objective To detect protein expression of ERK1,ERK2,JNK1,p38 and MEK1, MEK2 in human hepatocellular carcinoma and adjacent non-neoplastic liver.Methods In 16 surgically resected hepatocellular carcinoma and para-carcinoma tissues,Western blotting was used to detect expression of ERK1,ERK2,JNK1,p38 and MEK1,MEK2.Results In all cases,ERK1,ERK2,p38 expression in hepatocellular carcinoma was significantly higher than that in para-carcinoma:integral optic density (IOD) of ERK1 was 300±98 in carcinoma and 98±48 in para-carcinoma tissues (t=2.519,P<0.01);IOD of ERK2 was 587±83 in carcinoma and 232±96 in para-carcinoma tissues (t=2.745,P<0.01);IOD of p38 was 270±85 in carcinoma and 107±88 in para-carcinoma tissues (t=2.491,P<0.01).JNK1 expression in hepatocellular carcinoma was significantly lower than that in para-carcinoma;IOD of JNK1 was 111±93 in carcinoma and 292±109 in para-carcinoma tissues (t=2.473,P<0.01).Protein levels of MEK1 and MEK2 in carcinoma were significantly higher than in para-carcinoma.IOD of MEK1 was 1 418±244 in carcinoma and 806±90 in para-carcinoma tissues (t=2.546,P<0.01).IOD of MEK2 was 1 041±122 in carcinoma and 468±40 in para-carcinoma tissues (t=2.861,P<0.01).Conclusions ERK1,ERK2,MEK1 and MEK2 in the signal transduction pathway for cell proliferation are significantly overexpressed and the expression of JNK1 is lower in hepatocellular carcinoma.Their unbalance is one of the important reasons for the over growth and infinite proliferation of the hepatocellular carcinoma cell.The p38 and JNK1 may be activated by different pathway.中文核心期刊要目总览(PKU)中国科学引文数据库(CSCD)011-44