Downregulation of mitogen-activated protein kinases in human colon cancers

Background. Activation of the mitogen-activated protein kinases (MAPKs) app ears to play an important role in both proliferation and transformation of various cells; the role of MAPK activation in colorectal cancers has not be en clearly defined. The purpose of our study was to determine whether MAPK activity and protein levels were increased in colorectal cancers. Methods. Color-ectal cancers and adjacent normal mucosa from 21 patients were extrac ted for protein. Expression levels and activity of the MAPKs (ERK1/2, JNK1, p38 and ERK3) were assessed by immunoblot analysis and in vitro kinase ass ays, respectively. In addition, changes in myelin basic protein (MBP) kinas e 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 aut ophosphorylation was identified specifically in the cancers by in-gel kinas e assays. Conclusions. Ow findings demonstrate that the constitutive activa tion of ERK1/2, JNK1 and p38 is not a feature of colorectal cancels. Moreov er; our in-gel kinase results suggest that protein kinases, other than the MAPKs assessed, may play a more crucial role in colon carcinogenesis.