Department of Gatroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
J Exp Clin Cancer Res. 2009 Jul 25;28(1):106. doi: 10.1186/1756-9966-28-106.
Genetic instability is known as a cause of oncogenesis. Though Rad18 is reported to function in a post replication mismatch repair system, the relation between the status of Rad18 and human tumorigenesis has not been described so far.
Mutation analysis of 34 human cancer cell lines and 32 non small cell lung cancer (NSCLC) tissues were performed by RT-PCR SSCP. Expression level of Rad18 was measured by real time RT-PCR. Stable transfectant was constructed for in vitro study.
No mutation was found in both cancer cell lines and NSCLC tissues. A single nucleotide polymorphism (SNP) at codon 302 was detected in 51.5% of the cell lines and 62.5% of NSCLC tissues. Interestingly, Rad18 was homozygously deleted in a pulmonary adenocarcinoma cell line PC3. Furthermore, there was no difference in the expression level of wild type Rad18 and Rad18 with SNP. The growth, cell morphology, sensitivity to anti-cancer drugs and in vitro DNA repair activity between wild type Rad18 and Rad18 with SNP revealed to have no difference in vitro.
Though the frequency of SNP was tended to be higher in NSCLC patients than healthy volunteers (57.7%), as the difference was not significant, we have concluded that there is no relation between Rad18 SNP and lung cancer development.
遗传不稳定性被认为是致癌的原因之一。虽然 Rad18 被报道在复制后错配修复系统中发挥作用，但 Rad18 的状态与人类肿瘤发生之间的关系尚未被描述。
通过 RT-PCR SSCP 对 34 个人类癌细胞系和 32 个非小细胞肺癌（NSCLC）组织进行突变分析。通过实时 RT-PCR 测量 Rad18 的表达水平。构建稳定转染体进行体外研究。
在癌细胞系和 NSCLC 组织中均未发现突变。在 51.5%的细胞系和 62.5%的 NSCLC 组织中检测到密码子 302 处的单核苷酸多态性（SNP）。有趣的是，在肺腺癌细胞系 PC3 中发现 Rad18 纯合缺失。此外，野生型 Rad18 和具有 SNP 的 Rad18 的表达水平没有差异。野生型 Rad18 和具有 SNP 的 Rad18 在体外的生长、细胞形态、对抗癌药物的敏感性和体外 DNA 修复活性没有差异。
尽管 SNP 的频率在 NSCLC 患者中比健康志愿者（57.7%）更高，但差异不显著，我们得出结论，Rad18 SNP 与肺癌发生之间没有关系。
