Naumann M, Savitskaia N, Eilert C, Schramm A, Kalthoff H, Schmiegel W
Medical Clinic IMBL, Ruhr-University Bochum, Bochum, Germany.
Gastroenterology. 1996 Apr;110(4):1215-24. doi: 10.1053/gast.1996.v110.pm8613012.
BACKGROUND & AIMS: Cell-cycle inhibitor and tumor-suppressor gene p16/MTS1 was found to be altered in a variety of human tumors. To directly investigate genetic alterations and expression of p16/MTS1 and p15/MTS2, this study surveyed pancreatic tumors.
Cell-cycle inhibitors were analyzed for genetic alterations and expression by polymerase chain reaction, DNA sequencing, reverse-transcription polymerase chain reaction, and Western blotting.
The analysis of pancreatic adenocarcinoma (19 cell lines and 3 xenografts) for p16/MTS1 and p15/MTS2 revealed homozygous deletions in 10 of 22 cases (46%) (7 cell lines and 3 xenografts) involving both genes. We show in these 7 cell lines as well as in 3 additional cases (10 of 19[53%]) loss of p16/MTS1 transcripts and in 2 further cases (12 of 19 [63%]) mutations leading to the loss of p16 protein. The frequency of mutations in p16/MTS1 was 56% (5 of 9). In contrast to p16/MTS1, p15/MTS2 transcripts were obtained in all cases exhibiting the p15/MTS2 gene (54%). Loss of expression was not observed for p27 and p18.
These results support that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behavior of this tumor type.
细胞周期抑制剂及肿瘤抑制基因p16/MTS1在多种人类肿瘤中存在改变。为直接研究p16/MTS1和p15/MTS2的基因改变及表达情况，本研究对胰腺肿瘤进行了调查。
通过聚合酶链反应、DNA测序、逆转录聚合酶链反应及蛋白质免疫印迹法分析细胞周期抑制剂的基因改变及表达情况。
对胰腺腺癌（19个细胞系和3个异种移植瘤）的p16/MTS1和p15/MTS2分析显示，22例中有10例（46%）（7个细胞系和3个异种移植瘤）存在纯合缺失，涉及这两个基因。我们发现，在这7个细胞系以及另外3例（19例中的10例[53%]）中p16/MTS1转录本缺失，在另外2例（19例中的12例[63%]）中存在导致p16蛋白缺失的突变。p16/MTS1的突变频率为56%（9例中的5例）。与p16/MTS1不同，在所有检测到p15/MTS2基因的病例（54%）中均获得了p15/MTS2转录本。未观察到p27和p18的表达缺失。
这些结果支持p16功能缺失可能与胰腺癌有关，且可能至少部分解释了这种肿瘤类型的侵袭性行为。
