一种细胞周期蛋白依赖性激酶抑制剂（p21（WAF1/CIP1））影响人肝癌细胞中的胸苷掺入。
A cyclin-dependent kinase inhibitor (p21(WAF1/CIP1)) affects thymidine incorporation in human liver cancer cells.
作者信息
Gong Y, Deng S, Zhang M, Wang G, Minuk G Y, Burczynski F
机构信息
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
出版信息
Br J Cancer. 2002 Feb 12;86(4):625-9. doi: 10.1038/sj.bjc.6600099.
p21(WAF1/CIP1) is a universal cyclin-dependent kinase inhibitor. To investigate the role of p21(WAF1/CIP1) in proliferation of human liver cancer cells, we examined the expression of p53, p21(WAF1/CIP1), cdk2 and cdk4 expression in two human liver cancer cell lines (HepG2 and PLC/PRF/5 cells). The effects of p21(WAF1/CIP1) on [(3)H]thymidine incorporation and cdks were also examined in these cells. HepG2 cells expressed all these proteins with lower level of cdk4. PLC/PRF/5 cells expressed the other proteins except p21(WAF1/CIP1). Transfection of p21(WAF1/CIP1) gene inhibited [(3)H]thymidine incorporation of both cells with different extent. Although the transfection of p21(WAF1/CIP1) did not affect cdk2 and cdk4 expression, it did reduce cdk2 kinase activity by 20%. These results suggest that: (a) p21(WAF1/CIP1) involved in DNA synthesis of human liver cancer cells; (b) p21(WAF1/CIP1) could be a target gene for the treatment of human hepatocellular carcinoma.
p21（WAF1/CIP1）是一种通用的细胞周期蛋白依赖性激酶抑制剂。为了研究p21（WAF1/CIP1）在人肝癌细胞增殖中的作用，我们检测了两种人肝癌细胞系（HepG2和PLC/PRF/5细胞）中p53、p21（WAF1/CIP1）、cdk2和cdk4的表达。还检测了p21（WAF1/CIP1）对这些细胞中[³H]胸腺嘧啶核苷掺入和细胞周期蛋白依赖性激酶（cdks）的影响。HepG2细胞表达所有这些蛋白，cdk4水平较低。PLC/PRF/5细胞表达除p21（WAF1/CIP1）以外的其他蛋白。p21（WAF1/CIP1）基因转染不同程度地抑制了两种细胞的[³H]胸腺嘧啶核苷掺入。虽然p21（WAF1/CIP1）转染不影响cdk2和cdk4的表达，但它确实使cdk2激酶活性降低了20%。这些结果表明：（a）p21（WAF1/CIP1）参与人肝癌细胞的DNA合成；（b）p21（WAF1/CIP1）可能是治疗人肝细胞癌的一个靶基因。
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