Expression and activity of mitogen activated protein kinases in human colorectal carcinoma.
BACKGROUND
Mitogen activated protein kinases (MAPKs) play a central role in the regulation of both cell growth and differentiation. They are involved in signal transduction of oncogenes and growth factors. The role of MAPK in colonic carcinoma is unknown.


OBJECTIVE
To establish whether the expression and activity of p42/44 MAPKs are altered in colorectal tumours as compared with normal mucosa.


METHODS
The expression and activity of p42/p44 MAPK were investigated in 22 colorectal carcinomas, four adenomas, and the corresponding normal colorectal mucosa by the use of western blotting, immunoprecipitation, and in vitro kinase assays.


RESULTS
After immunoprecipitation with an antibody specific for p42 MAPK, we found significant inactivation of p42 MAPK in colonic carcinomas as well as in adenomas, whereas most sample pairs showed only minor differences in p42 MAPK expression. Investigation of MAPK with an antibody capable of detecting both p42 and p44 MAPK showed a slight but significant decrease in p44 MAPK content in malignant tissues. With this antibody, only minor alterations in MAPK activity and no correlation with p42 MAPK activity were found.


CONCLUSIONS
Inactivation of p42 MAPK could be associated with colonic carcinogenesis.
D000236:Adenoma / Q000201:enzymology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002277:Carcinoma / Q000201:enzymology*; D003106:Colon; D015179:Colorectal Neoplasms / Q000201:enzymology*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009363:Neoplasm Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D012007:Rectum