Takakura S, Kohno T, Shimizu K, Ohwada S, Okamoto A, Yokota J
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Oncogene. 2000 Feb 10;19(6):836-40. doi: 10.1038/sj.onc.1203388.
Recently, we found nonsense and missense mutations of the PPP1R3 (protein phosphatase 1, regulatory subunit 3) gene in diverse human cancer cell lines and primary lung carcinomas, indicating that PPP1R3 functions as a tumor suppressor in human carcinogenesis. In this study, to assess the prevalence of PPP1R3 mutations in human primary cancers and the genetic diversity of the PPP1R3 gene in the human population, somatic mutations and genetic polymorphisms in the PPP1R3 gene were examined in 137 pairs of cancerous and non-cancerous tissues of patients with cancers of colon, ovary, and liver. Five somatic mutations including two missense mutations were detected in three cancerous tissues consisting of two colorectal carcinomas and one ovarian carcinoma. Five novel single nucleotide polymorphisms (SNPs) associated with the substitution of amino acids were also identified in cancer patients, in addition to five known nonsynonymous SNPs, including three previously reported ones as having an impact on the susceptibility to insulin resistant disorders. Differences in the activities and properties of multiple PPP1R3 proteins, which are produced in human cells due to variable somatic mutations and genetic polymorphisms in the PPP1R3 gene, can be involved in human carcinogenesis and susceptibility to diseases.
最近，我们在多种人类癌细胞系和原发性肺癌中发现了PPP1R3（蛋白磷酸酶1调节亚基3）基因的无义突变和错义突变，这表明PPP1R3在人类致癌过程中发挥肿瘤抑制作用。在本研究中，为了评估PPP1R3突变在人类原发性癌症中的发生率以及该基因在人群中的遗传多样性，我们检测了137对结肠癌、卵巢癌和肝癌患者癌组织及癌旁组织中PPP1R3基因的体细胞突变和基因多态性。在由2例结直肠癌和1例卵巢癌组成的3个癌组织中检测到5个体细胞突变，其中包括2个错义突变。除了5个已知的非同义单核苷酸多态性（SNP）外，还在癌症患者中鉴定出5个与氨基酸替代相关的新型SNP，其中包括3个先前报道的对胰岛素抵抗性疾病易感性有影响的SNP。由于PPP1R3基因中可变的体细胞突变和基因多态性，在人类细胞中产生的多种PPP1R3蛋白的活性和特性差异可能与人类致癌作用和疾病易感性有关。
