Fang Wenzheng, Qian Jianxin, Wu Qing, Chen Ying, Yu Guanzhen
Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China; Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian Province, People's Republic of China.
Department of Medical Oncology, East Hepatobiliary Surgery Hospital, Shanghai, People's Republic of China.
J Surg Res. 2017 Dec;220:223-233. doi: 10.1016/j.jss.2017.06.032. Epub 2017 Aug 2.
The ADAMs proteases are a multifunctional family of proteins, many of which participate in the pathogenesis of cancers. The expression and regulation of ADAMs has not yet been fully examined in gastric cancer.
Using reverse transcription-PCR, messenger RNA expression of ADAM-9, ADAM-10, ADAM-11, ADAM-12, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 was detected in gastric cancer. ADAM-10, ADAM-17, ADAM-28, and FoxM1 expression in gastric cancer was detected by Western blot and immunohistochemistry. The correlation between ADAM-17 and FoxM1 was analyzed in vivo and in vitro.
The messenger RNA levels of ADAM-9, ADAM-10, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 were increased in tumor tissues compared with adjacent normal tissue, especially ADAM-10, ADAM-17, and ADAM-28. FoxM1 expression correlated significantly with ADAM-17 expression. FoxM1 regulates ADAM-17 expression in vivo and in vitro, which in turn influences proliferation and tumor growth of gastric cancer cells. Furthermore, Cox regression analysis revealed that FoxM1 and ADAM-17 are independent prognostic factors for patients with gastric cancer.
These results indicate that overexpression of ADAMs may contribute to gastric cancer progression and that ADAM-17 is a downstream target of FoxM1. Overall, the present study highlights the potential for FoxM1 and ADAMs as potential therapeutic targets for patients with gastric carcinoma.
ADAMs蛋白酶是一类多功能蛋白质家族，其中许多成员参与癌症的发病机制。ADAMs在胃癌中的表达和调控尚未得到充分研究。
采用逆转录聚合酶链反应（RT-PCR）检测胃癌组织中ADAM-9、ADAM-10、ADAM-11、ADAM-12、ADAM-15、ADAM-17、ADAM-28和ADAM-33的信使核糖核酸（mRNA）表达。通过蛋白质免疫印迹法（Western blot）和免疫组织化学法检测胃癌组织中ADAM-10、ADAM-17、ADAM-28和叉头框蛋白M1（FoxM1）的表达。在体内和体外分析ADAM-17与FoxM1之间的相关性。
与癌旁正常组织相比，肿瘤组织中ADAM-9、ADAM-10、ADAM-15、ADAM-17、ADAM-28和ADAM-33的mRNA水平升高，尤其是ADAM-10、ADAM-17和ADAM-28。FoxM1表达与ADAM-17表达显著相关。FoxM1在体内和体外均调控ADAM-17的表达，进而影响胃癌细胞的增殖和肿瘤生长。此外，Cox回归分析显示，FoxM1和ADAM-17是胃癌患者的独立预后因素。
这些结果表明，ADAMs的过表达可能促进胃癌进展，且ADAM-17是FoxM1的下游靶点。总体而言，本研究突出了FoxM1和ADAMs作为胃癌患者潜在治疗靶点的可能性。
