Miki H, Yamada H, Mitamura K
Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Anticancer Res. 1999 Nov-Dec;19(6B):5283-91.
Mitogen-activated protein kinases (MAPKs) have been thought to be involved in tumor development, and recently implicated in the regulation of apoptosis. We assessed the activation of p38 MAPK and extracellular signal-regulated kinases (ERKs) in human colorectal adenocarcinoma by immunoblotting with antibodies raised against each activated form. We also assessed the alteration of proliferative and apoptotic states, and analyzed the association of p38 MAPK with these alterations. The incidence of p38 MAPK activation in the cancer nucleus was significant (p = 0.0215), while ERKs activation was not significant. Proliferating cell nuclear antigen (PCNA)-labeling index and apoptotic index were increased in all cancer tissues. These findings suggested that p38 MAPK was constitutionally activated and was associated with increased proliferative and apoptotic states in colorectal cancers. Serum-deprivation-induced apoptosis in colonic adenocarcinoma cell line was significantly inhibited by SB203580, a specific p38 MAPK inhibitor, suggesting that apoptosis was mediated by the p38 MAPK pathway.
丝裂原活化蛋白激酶（MAPKs）被认为参与肿瘤发展，且最近发现其与细胞凋亡调控有关。我们通过用针对每种活化形式产生的抗体进行免疫印迹，评估了人结肠腺癌中p38 MAPK和细胞外信号调节激酶（ERKs）的活化情况。我们还评估了增殖和凋亡状态的改变，并分析了p38 MAPK与这些改变的关联。癌细胞核中p38 MAPK活化的发生率显著（p = 0.0215），而ERKs活化不显著。所有癌组织中增殖细胞核抗原（PCNA）标记指数和凋亡指数均升高。这些发现表明，p38 MAPK在结肠直肠癌中持续活化，并与增殖和凋亡状态增加有关。特异性p38 MAPK抑制剂SB203580显著抑制了结肠腺癌细胞系中血清剥夺诱导的细胞凋亡，提示细胞凋亡是由p38 MAPK途径介导的。
