SIAH1核异位表达抑制乳腺癌细胞凋亡的作用机制

Mechanism Underlying the Inhibition of Breast Cancer Cell Apoptosis by Ectopic Nuclear Expression of SIAH1

目的探讨SIAH1核异位表达抑制乳腺癌细胞凋亡的分子机制。方法应用免疫组织化学染色及Western blotting方法检测乳腺癌细胞中SIAH1的表达。构建SIAH1核异位表达的乳腺癌细胞模型,应用免疫荧光及共聚焦实验分析乳腺癌细胞中SIAH1的表达定位情况,并采用流式细胞术、siRNA干扰技术分析乳腺癌细胞的凋亡情况。结果 SIAH1在部分乳腺癌组织中存在核表达;乳腺癌组织中SIAH1核表达高于对应的癌旁正常组织(P <0.05)。S-亚硝基谷胱甘肽(GSNO)刺激乳腺癌细胞诱导SIAH1入核,从而抑制乳腺癌细胞凋亡。结论 GSNO诱导SIAH1核异位表达后可能通过下调E2F1/Bim的表达抑制乳腺癌细胞凋亡。

Objective To investigate the molecular mechanism underlying apoptosis inhibition of breast cancer cells through the ectopic expression of seven in absentia hmologue-1(SIAH1).Methods Immunohistochemistry and Western blotting were used to detect the expression of SIAH1 in breast cancer tissues.We constructed a model of SIAH1 nuclear ectopic expression in breast cancer cells.The location of SIAH1 was detected through immunofluorescence and confocal microscopy.Flow cytometry assay and siRNA interference were adopted to analyze cell apoptosis in breast cancer cells.Results SIAH1 was localized in the nucleus of breast cancer cell.The expression of SIAH1 in the nuclei of breast cancer tissues was higher than that in paired normal tissues(P<0.05).S-nitrosoglutathion(e GSNO)could induce SIAH1 to penetrate the nucleus,which,in turn,could inhibit the apoptosis of breast cancer cells.Conclusion The-induced heterotopic expression of SIAH1 can inhibit the apoptosis of breast cancer cells probably by reducing the expression of E2F1/Bim.