Sun Haoyao, Zou Shitao, Zhang Shuyu, Liu Biao, Meng Xingjun, Li Xiaoqing, Yu Jian, Wu Jinchang, Zhou Jundong
Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital Suzhou 215001, Jiangsu, P. R. China.
Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital Suzhou 215001, Jiangsu, P.R. China.
Int J Clin Exp Pathol. 2015 Apr 1;8(4):3591-601. eCollection 2015.
DNA polymerase iota (Polι) can repair several types of DNA damage but has extremely low fidelity. Previous studies have shown an aberrantly elevated Polι expression in human esophageal squamous cell cancer tissues. However, there were few reports describing the role of Polι in esophageal cancer progression. Based on Real-time PCR assay, we found Polι expression was up-regulated in esophageal cancer tissues compared to adjacent normal tissues and overexpression of Polι was correlated to lymph node metastasis. Clonogenic assay and transwell chamber assay showed that overexpression of Polι had higher clongenic capability and invasive tendency in human esophageal squamous cell cancer cells. Expression of cyclin D1, an important cell cycle regulator, was found to be associated with that of Polι in tissue samples and cancer cells as analyzed by real-time PCR, immunohistochemistry, Western blotting and immunofluorescence assay. Flow cytometry analysis further showed that cell cycle distribution was altered in Polι overexpressing cells. These results indicated that expression of Polι correlates significantly with tumor proliferation and invasion. We conclude that Polι is involved in the degree of aggressiveness of human esophageal squamous cell cancer.
DNA聚合酶ι(Polι)可修复多种类型的DNA损伤,但保真度极低。先前的研究表明,Polι在人食管鳞状细胞癌组织中的表达异常升高。然而,关于Polι在食管癌进展中作用的报道较少。基于实时PCR分析,我们发现与相邻正常组织相比,食管癌组织中Polι的表达上调,且Polι的过表达与淋巴结转移相关。克隆形成试验和Transwell小室试验表明,Polι的过表达在人食管鳞状细胞癌细胞中具有更高的克隆形成能力和侵袭倾向。通过实时PCR、免疫组织化学、蛋白质印迹和免疫荧光分析发现,组织样本和癌细胞中重要的细胞周期调节因子细胞周期蛋白D1的表达与Polι的表达相关。流式细胞术分析进一步表明,Polι过表达细胞中的细胞周期分布发生了改变。这些结果表明,Polι的表达与肿瘤增殖和侵袭显著相关。我们得出结论,Polι参与了人食管鳞状细胞癌的侵袭程度。