内质网应激相关因子PERK和ATF6在结肠癌中的表达及意义

Expression and significance of endoplasmic reticulum stress chaperone PERK and ATF6 in colon cancer

目的探讨内质网应激相关因子蛋白激酶R样内质网调节激酶(PERK)和活化转录因子6(ATF6)在结直肠癌组织中的表达情况,分析PERK和ATF6在结肠癌发生发展中的作用。方法选择手术切除结肠癌组织及距离病变组织5 cm以上正常组织,采用实时荧光定量PCR技术(RTPCR)检测PERK和ATF6的mRNA表达情况,免疫组织化学法(IHC)、Western blot法检测PERK和ATF6蛋白的表达情况,并结合临床病理特征,分析其与结肠癌发生、发展之间的关系。结果肿瘤组织ATF6和PERK mRNA表达均较正常组织下调(P<0.05)。IHC和Western blot结果显示PERK和ATF6在结肠癌中的表达均显著低于正常组织(P<0.05)。PERK和ATF6主要定位于上皮细胞中。结论PERK和ATF6在结肠癌中的表达水平下降说明缺乏适当的内质网应激反应可能在肿瘤的发生机制中起作用。

Objective To explore the expression of endoplasmic reticulum （ER） stress chaperone pancreatic ERkinase-like ER kinase （PERK） and activating transcription factor 6 （ATF6） in human colon cancer. Methods Curative tissues of colon cancer and tumor-adjacent tissues more than 5 cm away from lesioned tissues were collect- ed from the First Affiliated Hospital of Henan University of Science and Technology from September. PERK and ATF6 mRNA level was detected by real-time quantitative PCR （RT-PCR）, immunohistochemistry （IHC） and Western blot were used to detect protein levels of PERK and ATF6. The relationship of the clinical pathological fea- tures of these patients with expression of PERK or ATF6 was analyzed. Results PERK and ATF-6 mRNA were down-regulated in cancer tissues compared to their corresponding tumor-adjacent tissues （P 〈 0. 05）. In consistent with gene expression, PERK and ATF6 protein were also down-regulated in colon cancer （ P 〈 0. 05 ）.IHC showed that PERK and ATF6 were mainly located in the cytoplasm of colonic epithelial cells. Conclusion ER stress was involved in the tumorigenesis of colon cancer.