Arap W, Nishikawa R, Furnari F B, Cavenee W K, Huang H J
Ludwig Institute for Cancer Research, La Jolla, CA 92093-0660.
Cancer Res. 1995 Mar 15;55(6):1351-4.
The p16/CDKN2 gene has many features of a growth suppressor gene: it maps to 9p21, a frequent region of loss of heterozygozity in a variety of tumor types; it encodes an inhibitor of cyclin-dependent kinase 4; and its homozygous deletion is common in tumor-derived cell lines. However, the lower frequency of alteration of the gene in primary tumor tissue as compared to the cognate tumor cell lines has brought this interpretation into question. We have assessed the growth suppressive function of p16/CDKN2 by gene transfer. The introduction of full-length p16/CDKN2 cDNA caused marked growth suppression in p16/CDKN2-null human glioma cells, but was without significant effect in those cells with endogenous wild-type p16/CDKN2 alleles. These results provide functional evidence in support of the hypothesis that the p16/CDKN2 gene is a functional growth suppressor gene, at least in gliomas.
p16/CDKN2基因具有生长抑制基因的许多特征：它定位于9p21，这是多种肿瘤类型中常见的杂合性缺失区域；它编码细胞周期蛋白依赖性激酶4的抑制剂；其纯合缺失在肿瘤衍生细胞系中很常见。然而，与同源肿瘤细胞系相比，原发性肿瘤组织中该基因的改变频率较低，这使得这种解释受到质疑。我们通过基因转移评估了p16/CDKN2的生长抑制功能。全长p16/CDKN2 cDNA的导入在p16/CDKN2缺失的人胶质瘤细胞中引起了显著的生长抑制，但对那些具有内源性野生型p16/CDKN2等位基因的细胞没有显著影响。这些结果提供了功能证据，支持p16/CDKN2基因是一种功能性生长抑制基因的假说，至少在胶质瘤中是如此。
