[RB gene expression in gastrointestinal tract].
pRB, the retinoblastoma tumor suppressor gene product, regulates the cell cycle at G1/S transition negatively. Many cell cycle regulators modulate pRB function through its phosphorylation status. G1 cyclins (cyclin D, E)/cyclin-dependent kinases (cdk2, 4) inactivates pRB through its phosphorylation, while p21 (WAF1) and p16 inhibit cdks. In several kinds of cancer, Rb gene alteration or functional inactivation of pRB has been reported. In esophageal cancer, loss of heterozygosity of Rb gene and cyclin D gene amplification were frequently detected. But in gastric and colorectal cancer, Rb gene loss or deletion has been shown to be rare. In this study we investigated the expression of pRB, G1 cyclins, cdks and cdk-inhibitors in adenoma-carcinoma sequence of colorectum. And we compared the phosphorylation status of pRB in colorectal normal mucosa and cancer tissue. In adenoma only cyclin D and E were overexpressed but not cdks. In cancer in adenoma pRB and cdk2 were overexpressed with high frequency, and cdk4 overexpression was detected in advanced cancer. p16 overexpression was detected in almost all cancers, but in contrast p21 overexpression was rare event. Comparative study showed that pRB-positive cancer cells also expressed both cdc2/cdk2 and cyclin E. Densitometric analysis revealed that in advanced cancer pRB was hyperphosphorylated compared with normal mucosa. These results indicate that overexpression of cyclin D/cdk4 and cyclin E/cdk2 would phosphorylate pRB, and insufficient expression of p21 may accelerate pRB inactivation.
Monden
T
T
Department of Surgery II, Osaka University Medical School.
Yamamoto
H
H
Ikeda
K
K
Izawa
H
H
Tsujie
M
M
Ohnishi
T
T
Miyoshi
Y
Y
Sekimoto
M
M
Tomita
N
N
Monden
M
M
D002453:Cell Cycle; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism / Q000502:physiology
D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases