Sato Kiyoshi, Tamura Gen, Tsuchiya Takashi, Endoh Yasushi, Sakata Ken, Motoyama Teiichi, Usuba Osamu, Kimura Wataru, Terashima Masanori, Nishizuka Satoshi, Zou Tongtong, Meltzer Stephen J
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Department of Surgery, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Virchows Arch. 2002 Feb;440(2):160-165. doi: 10.1007/s004280100499.
The PTEN tumor suppressor gene on 10q23.3, responsible for the Cowden and Bannayan-Zonana syndromes, encodes a dual-specificity phosphatase able to dephosphorylate both tyrosine phosphate and serine/threonine phosphate residues. Mutational inactivation of PTEN has been reported in various malignancies, including endometrial cancers, ovarian cancers, and glioblastomas. In this study, we investigated PTEN gene mutations in 10 gastric cancer cell lines and 58 primary gastric cancers by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP). Hypermethylation of promoter region CpG islands, an alternative mechanism of gene inactivation to coding region mutations, was also evaluated by methylation specific PCR (MSP). Only one (1.7%) of the 58 primary tumors carried a somatic 5-bp deletion in intron 7 of PTEN, which did not alter the mRNA sequence, and no mutations were detected in any of the cell lines. Similar levels of PTEN mRNA expression were observed in all cell lines and primary tumors studied by RT-PCR, and PTEN promoter CpG islands remained unmethylated. Therefore, we conclude that PTEN does not participate in gastric carcinogenesis as a tumor suppressor gene.
位于10q23.3的PTEN肿瘤抑制基因与考登综合征和巴纳扬-佐纳纳综合征相关，它编码一种双特异性磷酸酶，能够使酪氨酸磷酸化残基和丝氨酸/苏氨酸磷酸化残基去磷酸化。PTEN的突变失活已在包括子宫内膜癌、卵巢癌和胶质母细胞瘤在内的多种恶性肿瘤中被报道。在本研究中，我们通过聚合酶链反应单链构象多态性（PCR-SSCP）研究了10种胃癌细胞系和58例原发性胃癌中的PTEN基因突变情况。启动子区域CpG岛的高甲基化是一种不同于编码区突变的基因失活机制，我们也通过甲基化特异性PCR（MSP）对其进行了评估。58例原发性肿瘤中只有1例（1.7%）在PTEN基因内含子7发生了一个体细胞5碱基缺失，该缺失未改变mRNA序列，且在任何细胞系中均未检测到突变。通过逆转录-聚合酶链反应（RT-PCR）在所有研究的细胞系和原发性肿瘤中观察到相似水平的PTEN mRNA表达，且PTEN启动子CpG岛保持未甲基化状态。因此，我们得出结论，PTEN作为肿瘤抑制基因不参与胃癌的发生。
