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


METHODS
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.
Sakakura
C
C
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Hagiwara
A
A
Shirahama
T
T
Nakanishi
M
M
Yasuoka
R
R
Fujita
Y
Y
Inazawa
J
J
Abe
T
T
Kohno
M
M
Yamagishi
H
H
D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009367:Neoplasm Staging; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
D020928:Mitogen-Activated Protein Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)