Reduced p21(WAF1/CIP1) expression and p53 mutation in hepatocellular carcinomas.
p21(WAF1/CIP1) is a universal cyclin-dependent kinase (cdk) inhibitor, the expression of which is regulated by p53-dependent and p53-independent pathways. We examined p21(WAF1/CIP1) expression in and p53 status of 21 primary hepatocellular carcinomas (HCCs) by reverse-transcriptase polymerase chain reaction (RT-PCR) and by PCR single-strand conformation polymorphism (PCR-SSCP) analysis. p21(WAF1/CIP1) messenger RNA expression was reduced markedly in 8 of 21 HCCs (38.1%) and 5 of these 8 HCCs bore p53 mutations. The relative p21(WAF1/CIP1) messenger RNA expression value of HCCs with p53 mutations (.73 +/- .13 U, n = 6) was significantly lower than that of HCCs with wild-type p53 (1.00 +/- 0.21 U, n = 14; P < .01). The p21(WAF1/CIP1) expression levels in cancerous tissues (.73 +/- .13 U) were significantly reduced in comparison with those in noncancerous tissues (.97 +/- .13 U) (P < .01) in the 6 cases with p53 mutations. These data indicate that p21(WAF1/CIP1) expression in HCCs is predominantly regulated by dependence on p53 and that reduced p21(WAF1/CIP1 expression may participate in hepatocarcinogenesis.
Hui
A M
AM
Pathology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Kanai
Y
Y
Sakamoto
M
M
Tsuda
H
H
Hirohashi
S
S
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000737:chemistry*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D012333:RNA, Messenger