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 levels 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.
Wang
Q
Q
Department of Surgery, University of Texas Medical Branch Galveston, USA.
Ding
Q
Q
Dong
Z
Z
Ehlers
R A
RA
Evers
B M
BM
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D048051:p38 Mitogen-Activated Protein Kinases
D009363:Neoplasm Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3