Amplified CDK2 and cdc2 activities in primary colorectal carcinoma.
BACKGROUND
Cyclins are overexpressed in various malignancies, including carcinoma of the colorectum, esophagus, lung, larynx, and breast. However, to the authors' knowledge, the protein levels and activities of cyclin-dependent kinases (CDKs), which are the functional cyclin partners in the cell cycle, have not been investigated previously.


METHODS
Eight samples of cancer tissue and adjacent normal tissue were taken from 23 patients with Stage B2-C1 (AJCC/UICC Stage II-III) colorectal carcinoma during curative resection. The protein levels of cyclin and CDKs were determined by Western blot analysis. The activities of CDKs were determined by the phosphorylation amount using specific substrates after immunoprecipitations.


RESULTS
The protein expression of cyclin (D1, D3, E, and A) and CDKs (CDK4, CDK2, and cdc2) was higher in primary colorectal carcinoma tissue than in adjacent normal tissue. Whereas only 3 of 8 patients had increased CDK4 activity in cancer tissue, 8 of 8 and 7 of 8 patients had increased CDK2 and cdc2 activities, respectively, in cancer tissue compared with adjacent normal tissue. However, there were no positive correlations among the pathologic staging or differentiation status and the increased ratio of cyclin protein, CDK protein, or CDK activity.


CONCLUSIONS
These results indicate that significant activation of S and M phases of the cell cycle occurs in primary colorectal carcinoma.
Kim
J H
JH
Department of General Surgery, Chonbuk National University Medical School, Chonju, Republic of Korea.
Kang
M J
MJ
Park
C U
CU
Kwak
H J
HJ
Hwang
Y
Y
Koh
G Y
GY
D000368:Aged; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases