FBXW7α对结直肠癌细胞中热休克转录因子1表达和定位的影响  

Effects of FBXW7αon Expression and Localization of Heat Shock Transcription Factor 1 in Colorectal Cancer Cells

作　　者：孙傲 焦寒 付杰军[1] SUN Ao;JIAO Han;FU Jiejun(Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education,Center for Translational Medicine&School of Preclinical Medicine,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学长寿与老年相关疾病教育部重点实验室,转化医学研究中心,基础医学院,南宁530021

出　　处：《肿瘤防治研究》2021年第5期457-463,共7页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金(81560483,82060532);教育部留学回国人员科研启动基金;广西自然科学基金(2018GXNSFAA281177)。

摘　　要：目的探讨FBXW7对结直肠癌细胞中热休克转录因子1(HSF1)表达和定位的影响。方法Western blot法检测敲除FBXW7及WT的结直肠癌细胞系HCT116和DLD1中HSF1及pHSF1Ser326蛋白的表达;免疫荧光和Western blot检测在热休克及恢复期细胞中pHSF1Ser326的核蛋白表达和定位。结果过表达FBXW7α的DLD1细胞中HSF1蛋白表达显著降低(P<0.01);敲除FBXW7的HCT116和DLD1细胞中HSF1和pHSF1Ser326总蛋白表达显著升高(均P<0.05)。与WT组比较,敲除FBXW7的细胞中HSF1和pHSF1Ser326主要累积在细胞核,而胞质表达较弱;温热刺激后,WT细胞中HSF1及pHSF1Ser326表达恢复至未刺激水平,而敲除FBXW7的细胞中HSF1及pHSF1Ser326在核中有较强表达(均P<0.01)。结论敲除FBXW7的结直肠癌细胞热刺激后,细胞核HSF1水平恢复受阻,可能与缺失FBXW7不能降解胞核HSF1有关。Objective To investigate the effect of FBXW7 on the expression and localization of HSF1 in colorectal cancer cells.Methods The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 deletion(KO)and wild-type(WT)FBXW7-expressing counterpart colorectal cancer cells were detected by Western blot.The nucleoprotein expression and localization of pHSF1Ser326 in heat-shocked or recovery stage cells were observed by Western blot and immunofluorescence method.Results The HSF1 expression level in DLD1 cells transfected with FBXW7αwas decreased significantly(P<0.01).The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 KO cells were higher than those in WT cells(all P<0.05).HSF1 and pHSF1Ser326 in FBXW7 KO cells were mainly expressed in nucleus and weakly expressed in cytoplasm.After warm stimulation,the expression of HSF1 and pHSF1Ser326 in WT cells recovered to the unstimulated level,while the expression of HSF1 and pHSF1Ser326 in FBXW7 KO cells were higher in the nucleus(all P<0.01).Conclusion Loss of FBXW7 could affect the nuclear HSF1 recovery after warm stimulation.It may be associated with FBXW7 deletion inhibiting the degradation of nuclear HSF1.

关 键 词：FBXW7 热休克转录因子1 结直肠癌细胞 热休克反应 

分 类 号：R735.3[医药卫生—肿瘤]