Fujishita T, Mizushima Y, Kashii T, Kobayashi M
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Anticancer Res. 1998 May-Jun;18(3A):1537-42.
Cyclin-dependent kinase (CDK) inhibitor genes have recently been proposed as new tumor suppressor genes. To define the possible participation of CDK inhibitor genes in lung carcinogenesis, we investigated the alterations of p15INK4B, p16INK4A, p21Waf1, and p27Kip1 genes in 34 human lung cancer cell lines using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing, and southern dot blot methods. Among the four CDK inhibitor genes, alterations of only the p16INK4A gene were found in 8 out of 34 (24%) cell lines, and all eight cell lines having a p16INK4A gene alteration had an alteration of either the K-ras of p53 gene. Conversely, p16INK4A gene alterations were found in none of the 3 cell lines having Rb gene alterations and none of the 3 cell lines having amplification of the N-myc gene. Polymorphism was found in both p21Waf1 and p27Kip1 genes, but no association was found between the polymorphism and alterations of other genes. These results suggest that p16INK4A gene alterations may play a certain role for lung carcinogenesis in co-operation with either K-ras or p53 gene alterations.
细胞周期蛋白依赖性激酶（CDK）抑制基因最近被认为是新的肿瘤抑制基因。为了确定CDK抑制基因在肺癌发生中的可能作用，我们采用聚合酶链反应-单链构象多态性（PCR-SSCP）、直接测序和Southern斑点杂交方法，研究了34个人类肺癌细胞系中p15INK4B、p16INK4A、p21Waf1和p27Kip1基因的改变情况。在这四个CDK抑制基因中，仅在34个细胞系中的8个（24%）发现了p16INK4A基因的改变，并且所有8个有p16INK4A基因改变的细胞系都有K-ras或p53基因的改变。相反，在3个有Rb基因改变的细胞系和3个有N-myc基因扩增的细胞系中均未发现p16INK4A基因改变。在p21Waf1和p27Kip1基因中均发现了多态性，但未发现该多态性与其他基因改变之间存在关联。这些结果表明，p16INK4A基因改变可能与K-ras或p53基因改变协同作用，在肺癌发生中发挥一定作用。
