Infrequent activation of mitogen-activated protein kinase in human colon cancers.

BACKGROUND/AIMS: Mitogen-activated protein kinase (MAPK) is a downstream factor of the Ras-Raf-MAPK cascade and it is now considered to be a key molecule in signaling processes stimulated by growth factors and differentiation inducers.

METHODOLOGY

We examined MAPK activity in 21 advanced colon cancers to investigate whether the MAPK cascade might play a role in the progression of colon cancers.

RESULTS

MAPK activation (3.9-10.1-fold) was observed in 4 of 21 cases (18%), but 3 cases (75%, 3 of 4 cases) showed MAPK activation without ras mutation, thus suggesting that MAPK activation did not correlate with the presence of Ki-ras mutations in these cases. Other kinds of oncogene activation would be involved to MAPK activation in human colon cancers. In other cases MAPK activation was not detected or partly down-regulated.

CONCLUSIONS

These findings suggest that positive and negative regulation of MAPK activity are associated with loss of normal growth control and may be involved in carcinogenesis of colon cancers.