α2,8-唾液酸转移酶Ⅵ过量表达影响小鼠乳腺癌细胞基因表达的研究

Study on the Effect of an Over-Expressed Sixth Type of α2,8-sialyltransferase(ST8Sia Ⅵ) on the Gene Expression of Murine Breast Cancer Cells

研究α2,8-唾液酸转移酶Ⅵ(Sixth type ofα2,8-sialyltransferase,ST8Sia Ⅵ)对乳腺癌细胞生物学功能的影响及其作用的分子机制。采用全基因组芯片技术检测ST8Sia Ⅵ过表达前后小鼠乳腺癌细胞4T1基因表达谱的差异;利用PathwayExplorer分析ST8Sia Ⅵ过表达前后对基因网络的影响。实验结果表明:ST8Sia Ⅵ过表达引起201个基因表达有差异,其中22个基因与肿瘤细胞的黏附、生长、运动、免疫和周期有关。另外,PathwayExplorer分析结果显示,差异表达基因涉及的最显著变化的基因网络是"依赖β-arrestin的G蛋白偶联受体(GPCR)信号通路";进一步的实验结果证明该通路下游Raf蛋白的磷酸化水平在ST8Sia Ⅵ过表达细胞显著升高。上述结果为ST8Sia Ⅵ生物学功能的深入研究提供了前提。

This study aimed at clarifying the roles and molecular mechanisms of the sixth type of sialyltransferase（ST8Sia VI） in breast cancer cells. In this study, the gene expression of 4T1 cells over-expressed ST8Sia VI and 4T1 cells transfeeted empty vector were compared by gene chip, and the related signal pathways of differentially expressed genes were determined based on the public databases with PathwayExplorer. The results showed that the expressions of 201 genes were differential in STSSia VI over-expressed cells and control cells, of which 22 genes were involved in cell adhesion, growth, locomotion, immune process and cell cycle. The genes expressed differentially were also involved in β-arrestindependent GPCR signaling pathway. In addition, Raf, a downstream member of β-arrestin-dependent GPCR signaling pathway, was found to be highly phosphorylated in 4T1-ST8Sia VI cells. These results lay the foundation for an in-depth study of STSSia VI.