有丝分裂蛋白激酶及其上游调节信号在人肝癌组织中的表达

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.

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

OBJECTIVE: To detect protein expression of ERK(1), ERK(2), JNK(1), p38 and MEK(1), MEK(2) 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 ERK(1), ERK(2), JNK(1), p38 and MEK(1), MEK(2). RESULTS: In all cases, ERK(1), ERK(2), p38 expression in hepatocellular carcinoma was significantly higher than that in para-carcinoma: integral optic density (IOD) of ERK(1) was 300 +/- 98 in carcinoma and 98 +/- 48 in para-carcinoma tissues (t = 2.519, P < 0.01); IOD of ERK(2) 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). JNK(1) expression in hepatocellular carcinoma was significantly lower than that in para-carcinoma; IOD of JNK(1) was 111 +/- 93 in carcinoma and 292 +/- 109 in para-carcinoma tissues (t = 2.473, P < 0.01). Protein levels of MEK(1) and MEK(2) in carcinoma were significantly higher than in para-carcinoma. IOD of MEK(1) was 1 418 +/- 244 in carcinoma and 806 +/- 90 in para-carcinoma tissues (t = 2.546, P < 0.01). IOD of MEK(2) was 1 041 +/- 122 in carcinoma and 468 +/- 40 in para-carcinoma tissues (t = 2.861, P < 0.01). CONCLUSIONS: ERK(1), ERK(2), MEK(1) and MEK(2) in the signal transduction pathway for cell proliferation are significantly overexpressed and the expression of JNK(1) 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 JNK(1) may be activated by different pathway.