Wang Xiao-Hong, Du Hong, Li Lin, Shao Duan-Fang, Zhong Xi-Yao, Hu Ying, Liu Yi-Qiang, Xing Xiao-Fang, Cheng Xiao-Jing, Guo Ting, Li Shen, Li Zi-Yu, Bu Zhao-De, Wen Xian-Zi, Zhang Lian-Hai, Ji Jia-Fu
Department of Tissue Bank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Oncol Lett. 2017 Jan;13(1):222-230. doi: 10.3892/ol.2016.5419. Epub 2016 Nov 22.
S100A6 is involved in regulating the progression of cancer. S100A6 can regulate the dynamics of cytoskeletal constituents, cell growth and differentiation by interacting with binding or target proteins. The present study investigated whether S100A6 affects cell proliferation in gastric cancer cells by stimulating several downstream factors. Firstly, the expression and localization of S100A6 were investigated using immunohistochemical staining, an immunoelectron microscopy and laser confocal scanning. A ChIP-Chip assay was performed to determine the downstream factors of S100A6 using promoter Chip analysis, including approximately the -800 to +200 regions around the transcription starting point. Polymerase chain reaction analysis was performed to confirm this. It was found that the intensity of S100A6 staining was markedly higher in the cytoplasm and nucleus, and its expression level correlated with that of the Ki67 protein. The overexpression of S100A6 also promoted cell proliferation in AGS and BGC823 cell lines, detected using a Cell Counting-Kit 8 assay. In cells overexpressing S100A6, the expression levels of interleukin (IL)-8, cyclin-dependent kinase (CDK)5, CDK4, minichromosome maintenance complex component 7 (MCM7) and B-cell lymphoma 2 (Bcl2) were noticeably increased. In conclusion, the increased expression of S100A6 promoted cell proliferation by regulating the expression levels of IL-8, CDK5, CDK4, MCM7 and Bcl2 in gastric cancer cells.
S100A6参与调控癌症进展。S100A6可通过与结合蛋白或靶蛋白相互作用来调控细胞骨架成分的动态变化、细胞生长和分化。本研究调查了S100A6是否通过刺激多个下游因子来影响胃癌细胞的增殖。首先,采用免疫组织化学染色、免疫电子显微镜和激光共聚焦扫描来研究S100A6的表达和定位。使用启动子芯片分析(包括转录起始点周围约-800至+200区域)进行染色质免疫沉淀芯片分析(ChIP-Chip),以确定S100A6的下游因子。进行聚合酶链反应分析以证实这一点。结果发现,S100A6在细胞质和细胞核中的染色强度明显更高,其表达水平与Ki67蛋白的表达水平相关。使用细胞计数试剂盒8检测发现,S100A6的过表达也促进了AGS和BGC823细胞系中的细胞增殖。在过表达S100A6的细胞中,白细胞介素(IL)-8、细胞周期蛋白依赖性激酶(CDK)5、CDK4、微小染色体维持复合物组分7(MCM7)和B细胞淋巴瘤2(Bcl2)的表达水平显著增加。总之,S100A6表达增加通过调节胃癌细胞中IL-8、CDK5、CDK4、MCM7和Bcl2的表达水平促进细胞增殖。