Zhang S, Endo S, Koga H, Ichikawa T, Feng X, Onda K, Washiyama K, Kumanishi T
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, Asahimachi-doori.
Jpn J Cancer Res. 1996 Sep;87(9):900-7. doi: 10.1111/j.1349-7006.1996.tb02118.x.
A total of 10 glioma cell lines were examined for alterations of the p16, p15, p53 and p21 genes, which are tumor suppressor genes or candidates with direct or indirect CDK-inhibitory functions. Genetic alterations (deletions or mutations) were frequently seen in the p16, p15 and p53 genes in these cell lines, but not in the p21 gene. When the states of the p16, p15 and p53 genes were compared among cell lines, all the cell lines showed abnormalities in at least 1 gene, often in 2 or 3 genes coincidentally, suggesting that dysfunction of these genes is closely related to glioma cell growth. Although alteration of all 3 genes was most frequent, there were cell lines having either p16/p15 or p53 or pl6 and p53 gene alterations, suggesting that the time order of these genetic alterations was variable depending on the cell line. Among cell lines examined, one with homozygous p53 gene deletion seemed of particular practical value, since such a cell line might be useful in various studies, including investigation of the functions of various mutant p53 genes in the absence of heteromeric protein formation. On examination of the primary tumor tissues, the same alterations of the p16/p15 and p53 genes as detected in the cell lines were demonstrated in all 6 cases examined: p16/p15 gene deletion in 1, p16 gene mutation in 1 and p53 gene mutations in 5 cases. This suggested that the p16/p15 and the p53 gene alterations and their combinations in at least some glioma cell lines reflected those in the primary glioma tissues.
共检测了10种胶质瘤细胞系中p16、p15、p53和p21基因的改变,这些基因是肿瘤抑制基因或具有直接或间接CDK抑制功能的候选基因。在这些细胞系中,p16、p15和p53基因经常出现基因改变(缺失或突变),但p21基因未出现。当比较各细胞系中p16、p15和p53基因的状态时,所有细胞系至少有1个基因异常,常同时有2个或3个基因异常,提示这些基因功能异常与胶质瘤细胞生长密切相关。虽然3个基因同时改变最为常见,但也有细胞系仅出现p16/p15或p53或p16和p53基因改变,提示这些基因改变的时间顺序因细胞系而异。在所检测的细胞系中,有1个细胞系p53基因纯合缺失似乎具有特别的实用价值,因为这样的细胞系可能在各种研究中有用,包括在不存在异源蛋白形成的情况下研究各种突变p53基因的功能。在对原发性肿瘤组织进行检测时,在所检测的所有6例病例中均发现了与细胞系中相同的p16/p15和p53基因改变:1例p16/p15基因缺失,1例p16基因突变,5例p53基因突变。这表明至少在一些胶质瘤细胞系中,p16/p15和p53基因改变及其组合反映了原发性胶质瘤组织中的情况。