Hui A M, Kanai Y, Sakamoto M, Tsuda H, Hirohashi S
Pathology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Hepatology. 1997 Mar;25(3):575-9. doi: 10.1002/hep.510250314.
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.
p21（WAF1/CIP1）是一种通用的细胞周期蛋白依赖性激酶（cdk）抑制剂，其表达受p53依赖性和p53非依赖性途径调控。我们通过逆转录聚合酶链反应（RT-PCR）和PCR单链构象多态性（PCR-SSCP）分析检测了21例原发性肝细胞癌（HCC）中p21（WAF1/CIP1）的表达及p53状态。21例HCC中有8例（38.1%）p21（WAF1/CIP1）信使核糖核酸表达明显降低，这8例中有5例存在p53突变。p53突变的HCC的相对p21（WAF1/CIP1）信使核糖核酸表达值（.73±.13 U，n = 6）显著低于野生型p53的HCC（1.00±0.21 U，n = 14；P <.01）。在6例p53突变的病例中，癌组织中的p21（WAF1/CIP1）表达水平（.73±.13 U）与非癌组织（.97±.13 U）相比显著降低（P <.01）。这些数据表明，HCC中p21（WAF1/CIP1）的表达主要受p53依赖性调控，p21（WAF1/CIP1）表达降低可能参与肝癌发生。
