摘要
目的:探讨Rac GTP酶激活蛋白1(Rac GTP ase activating protein1,Rac1)对胰腺癌细胞增殖的影响及其机制.方法:分别采用EDU和CCK-8(cell counting kit-8)方法检测Rac1对胰腺癌细胞增殖的影响;采用Western blot、免疫荧光等试验探讨Rac1影响胰腺癌增殖的具体机制.结果:Rac1可以促进胰腺癌细胞的增殖,沉默Rac1或者Rac1特异性阻滞剂NSC 23766可以抑制胰腺癌的增殖,且进一步的机制研究发现Rac1通过促进β-Catenin进入细胞核,上调wnt-β-Catenin信号通路靶基因c-myc、c-jun和Cyclin D1的表达,进而促进胰腺癌细胞的增殖.结论:Rac1通过wnt-β-Catenin信号通路促进胰腺癌细胞的增殖.
AIM： To investigate the role of rac1 in the proliferation of pancreatic carcinoma cells and to explore the possible mechanisms involved. METHODS： The influence of rac1 on the proliferation of pancreatic carcinoma cells was detected by cell counting kit-8 （CCK-8） assay and EDU assay. Real-time PCR was employed to measure the expression of target genes of wnt-β-Catenin signaling pathway. Western blot and immunofluorescence were employed to measure the expression of β-Catenin in the cytoplasm and nucleus.RESULTS： Disruption of rac1 activity by transfection with si-Rac1 or treatment with NSC23766 inhibited cell proliferation. Suppression of rac1 markedly down-regulated the mRNA expression of c-myc and Cyclin D1 and slightly decreased the mRNA expression of c-jun. Rac1 knockdown did not affect β-Catenin stability in the cytoplasm but markedly reduced β-Catenin accumulation in the nucleus. Similar result was also obtained in immunofluorescence experiments. CONCLUSION： Rac1 amplifies the wnt signaling pathway activity possibly by promoting β-Catenin accumulation in the nucleus and augments wnt target gene transcription in pancreatic carcinoma cells.
出处
《世界华人消化杂志》
CAS
北大核心
2013年第12期1070-1074,共5页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.81001068
No.81071775
关键词
RAC1
胰腺癌
增殖
Rac1
Pancreatic carcinoma
Proliferation
