HRD1与LAT1在胃癌细胞中表达水平研究及其相关性分析.DOC

HRD1与LAT1在胃癌细胞中表达水平研究及其相关性分析 彭俊璐 史良会皖南医学院弋矶山医院胃肠三科，芜湖，241000 【摘要】【目的】研究HRD1）与L型氨基酸转运载体1（L-type amino acid transporter 1LAT-1）在胃癌及癌旁正常细胞中的表达水平，探讨HRD1与LAT1在胃癌发生发展中的作用及其相互作用。应用免疫组化、RT-PCR及Western-blot方法检测62例胃癌及癌旁细胞中HRD1及LAT1表达水平。胃癌组织中HRD1蛋白表达水平明显高于癌旁正常组织，差异有统计学意义（P＜0.05）。胃癌组织中HRD1表达与分化程度、淋巴结转移和临床分期均无关（P＞0.05）。LAT1在胃癌组织中表达明显高于癌旁正常组织，肿瘤大小5cm组显著高于＜5cm组，在Ⅰ、Ⅱ期的表达水平显著高于Ⅲ、Ⅳ期（P＜0.05）。HRD1与LAT1的表达水平呈正相关（P＜0.05）。HRD1与LAT1在胃癌细胞中表达水平均高于癌旁正常细胞，提示HRD1与LAT1在胃癌的发生、发展中发挥重要的作用。 胃癌；泛素连接酶；氨基酸转运载体 Significance of ubiquitin ligase HRD1 and L-type amino acid transporter-1 expressed in human gastric carcinoma and the relationship between them Peng Junlu,Shi Lianghui Wannan Medical College Yijishan Hospital，Wuhu，241000 [ABSTRACT] Objective To investigate the expression of HRD1 and LAT1 in gastric carcinoma and analyze the relationship between their overexpression. Methods By using immunohistochemical SP method,Q-PCR and western-blot,research the expressions of Hrd1 and LAT1 protein in 62 cases of normal human cells and gastric carcinoma cells.Result Expression level of Hrd1 protein was significantly higher in human gastric carcinoma cells than that in normal human cells (P＜0.05). But not with histologic grade and lymph node metastasis ( P＞0.05).The expression of LAT1 was higher in human gastric carcinoma cells than that in normal human cells,stage Ⅲ-Ⅳ, tumor size≥5cm, were significantly higher than those in stage Ⅰ-Ⅱ, tumor size ＜5cm (P＜0.05). The higher expression of LAT1 was positive correlated to HRD1 in gastric carcinoma (P＜0.05). Conclusion HRD1 and LAT1 highly express in gastric carcinoma,they may play an important role in the growing of gastric carcinoma. 【Key words】gastric carcinoma, ubiquitin ligase, L-type amino acid transporter 是L型氨基酸转运载体中主要成员，主要负责转运一些大的、芳香族的、中性氨基酸，包括一些必须氨基酸[1]。研究表明，LAT-1在肝脏、骨髓、脑、胎盘等正常组织和癌细胞中大量表达，并对恶性肿瘤的不断增殖起着重要的作用[2]。泛素化途径是一种翻译后修饰，在细胞周期，细胞增殖，DNA复制及细胞凋亡的过程中扮演重要的角色[3]。是一种跨膜的环形泛素连接酶（E3 Ubiquitin ligase），最初是在酿酒酵母和哺乳动物细胞表达系统中被研究，发现其在内质网相关降解的蛋白质错误折叠中扮演重要角色[4]。有蛋白质谱的研究发现