Downregulation of mitogen-activated protein kinases in human colon cancers

Background. Activation of the mitogen-activated protein kinases (MAPKs) appears to play an important role in both proliferation and transformation of various cells; the role of MAPK activation in colorectal cancers has not been clearly defined. The purpose of our study was to determine whether MAPK activity and protein level were increased in colorectal cancers. Methods. Colorectal cancers and adjacent normal mucosa from 21 patients were extracted for protein. Expression levels and activity of the MAPKs (ERK1/2, JNK1, p38 and ERK3) were assessed by immunoblot analysis and in vitro kinase assays, respectively. In addition, changes in myelin basic protein (MBP) kinase activity and autophosphorylation were determined by in-gel kinase assays. Results. The activities of ERK1/2, JNK1 and p38 were downregulated in the majority of cancers; ERK3 kinase activity was increased in 10 of 21 cancers. The presence of proteins displaying increased MBP phosphorylation and autophosphorylation was identified specifically in the cancers by in-gel kinase assays. Conclusions. Our findings demonstrate that the constitutive activation of ERK1/2, JNK1 and p38 is not a feature of colorectal cancers. Moreover, our in-gel kinase results suggest that protein kinases, other than the MAPKs assessed, may play a more crucial role in colon carcinogenesis.