p21WAF1／CIPI基因导入对p53突变人肺癌细胞系生长特性的影响

目的 探讨含突变ｐ５３基因癌细胞系ｐ２１基因的抗肿瘤作用。方法 构建人ｐ２１表达重组子,导入ｐ５３基因突变的人肺癌ＰＧ细胞每当增产同表达ｐ２１的细胞系;然后观察其形态太生长特性的改变;ＣＤＫ４,ＰＣＮＡ水平;对基因毒性物的反应性。结果 在含ｐ５３基因突变的ＰＧ细胞内导入的性ｐ２１基因,其高表达ｐ２１约是ＰＧ细胞的６倍,转谬为薄等异型性降低;生长速度下降（５０％）,叠落生长不明显;在０．５％血甭条件

Effects of p21WAF1/CIP1 gene introduction on a human lung cancer cell line with p53 mutation

OBJECTIVE: To study the effects of p21WAF1/CIP1 gene expression on the biological hehavior of cancer cells with p53 gene mutation. METHODS: Expression of p21 vehicle was constructed and introduced into a human lung cancer cell ling PG with p53 gene mutation, the morphological and growth characteristics of the transfectant were then analysed. The CDK4 and PCNA levels were evaluated and the response to genotoxic agents were observed. RESULTS: The PG cells with mutant p53 were transfected with ectopic p21 gene which resulted in overexpression of p21 (6-fold of the control). The transfectants presented decreased nuclear irregularity and thinner membrane in nuclear atypia, with delayed growth rate and contact growth inhibition. The transfectant also displayed high serum requirement in culture and increased anchorage dependence. Both levels of CDK4 and PCNA were decreased. However, the cisplatin induced cell apoptosis was delayed. CONCLUSIONS: Expression of p21WAF1/CIP1 gene was effective in cancer suppression even in p53 gene mutation. This may have been achieved through lowering of CDK4 or PCNA levels and not involving the apoptosis mechanism. Activation of p21WAF1/CIP1 gene may be considered a bypass for restoration of p53 gene function in cancer cells with p53 gene mutation.