Involvement of p38 MAP kinase in apoptotic and proliferative alteration in human colorectal cancers.

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.