Coexpression of cdk2/cdc2 and retinoblastoma gene products in colorectal cancer.
The retinoblastoma gene (Rb gene) is a tumour-suppressor gene and its product (pRB) is known to act as a negative regulator of the cell cycle. Although lack of pRB expression resulting from gene alterations is considered to be responsible for the genesis of several human malignancies, increased expression of pRB has been demonstrated in a majority of colorectal cancer cases. In the present study, we investigated the expression of pRB as well as that of its related kinases, cdk2 and cdc2, in colorectal cancer, since these kinases have been reported to phosphorylate and inactivate pRB. Western blot analysis revealed that colorectal cancer expressed higher levels of cdk2 and cdc2 than did normal mucosa and that the ratio of the hyperphosphorylated form of pRB was higher in colorectal cancer. Furthermore, immunohistochemical studies showed that cdk2/cdc2 was expressed exclusively in the cancer cells positive for pRB. These results suggest that an increase in the expression of cdk2/cdc2 in colorectal cancer may have prevented pRB from braking the cell cycle through phosphorylation.
Yamamoto
H
H
Second Department of Surgery, Osaka University Medical School, Japan.
Monden
T
T
Ikeda
K
K
Izawa
H
H
Fukuda
K
K
Fukunaga
M
M
Tomita
N
N
Shimano
T
T
Shiozaki
H
H
Monden
M
M
D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000032:analysis / Q000096:biosynthesis*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D003106:Colon / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000096:biosynthesis*; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000096:biosynthesis*; D012016:Reference Values; D016160:Retinoblastoma Protein / Q000032:analysis / Q000096:biosynthesis*
D016160:Retinoblastoma Protein; 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