Liu Q, Yan Y X, McClure M, Nakagawa H, Fujimura F, Rustgi A K
Myriad Genetics, Inc., Salt Lake City, Utah 84108.
Oncogene. 1995 Feb 2;10(3):619-22.
MTS-1 is a candidate tumor suppressor gene on chromosome 9p21-22, a region frequently observed to have loss of heterozygosity in esophagus squamous cell carcinomas and pancreatic ductal adenocarcinomas. In order to determine whether MTS-1 sequences are deleted or mutated in cell lines derived from these cancers, we performed PCR amplification of MTS-1 exons 1 and 2. In this fashion, we found that 67% of esophagus squamous cancer cell lines have deletions of both exons 1 and 2, and 50% of pancreatic cancer cell lines have similar deletions. Furthermore, an additional 30% of pancreatic cancer cell lines harbored point mutations or microdeletions based on DNA sequencing. MTS-1 encodes p16, an inhibitor of cyclin-dependent kinase 4 (cdk4) which complexes with cyclin D1. Our data suggest that MTS-1 deletions and mutations may play an important role in the molecular pathogenesis of esophagus squamous cell and pancreatic cancers.
MTS-1是位于9号染色体p21-22区域的一个候选肿瘤抑制基因，在食管鳞状细胞癌和胰腺导管腺癌中，该区域常出现杂合性缺失。为了确定源自这些癌症的细胞系中MTS-1序列是否缺失或突变，我们对MTS-1外显子1和2进行了PCR扩增。通过这种方式，我们发现67%的食管鳞状癌细胞系外显子1和2均有缺失，50%的胰腺癌细胞系有类似缺失。此外，基于DNA测序，另有30%的胰腺癌细胞系存在点突变或微缺失。MTS-1编码p16，一种细胞周期蛋白依赖性激酶4（cdk4）的抑制剂，它与细胞周期蛋白D1形成复合物。我们的数据表明，MTS-1的缺失和突变可能在食管鳞状细胞癌和胰腺癌的分子发病机制中起重要作用。
