肝细胞癌中β-链接素基因突变及异常表达  

The β-catenin gene mutation and abnormal expression in HBV related hepatocellular carcinoma

作　　者：李毅清[1] 王慧[2] 张进祥[1] 滕云[2] 郑启昌[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院普外科,武汉430022 [2]华中科技大学同济医学院遗传教研室

出　　处：《中华实验外科杂志》2005年第9期1059-1061,i0002,共4页Chinese Journal of Experimental Surgery

摘　　要：目的检测乙型肝炎病毒(HBV)相关肝细胞癌(HCC)组织及癌旁组织中β链接素(βcatenin)基因第3外显子突变及其表达异常,探讨其在HBV相关肝细胞癌中的作用。方法采用聚合酶链单链构象多态性(PCRSSCP)、直接测序、逆转录聚合酶链反应(RTPCR)、免疫组织化学技术等方法,检测27例HBV相关肝细胞癌及27例癌旁组织βcatenin基因第3外显子点突变以及βcateninmRNA表达差异性。结果(1)HCC组织中,βcatenin基因第3外显子的点突变率约26%(7/27),分别为密码子37(TCT→TGT),丝氨酸→半胱氨酸;密码子45(TCT→TTT),丝氨酸→苯丙氨酸;密码子35(ATC→ATG),异亮氨酸→蛋氨酸。癌旁组织均未发现突变(P<0.05)。(2)βcateninmRNA在癌组织中的表达量明显高于癌旁组织(0.86±0.07比0.33±0.04,P<0.05)。(3)βcatenin蛋白在癌细胞胞浆及核内聚集。结论βcatenin基因第3外显子突变及βcatenin的过度表达对HBV相关肝细胞癌发生起到重要作用。Objective To study the mechanism of hepatocellular carcinoma （HCC） with hepatitis B virus （HBV） infection in relation to the mutation in exon 3 of β-catenin and its abnormal expression, Methods Mutations in exon 3 of β-catenin gene and differential expression of β-catenin gene in the primary lesion and para-cancerous tissues of 27 cases of HCC with HBV were investigated by the methods of PCR-SSCP, RT-PCR, direct sequencing and immunohistochemical technique, Btsults （1） 26 % （7/27） of primary tumor lesions carried β-catenin mutations, 6 occurred at the serine/threonine residues of the GSK-3βregion of β-catenin： 3 at condon 37 ： TCT（Ser）→TGT（Cys）, 3 at condon 45 ： TCT（Ser）→TTT （Phe）, and one at condon 35：ATC（lle）→ATG. No mutation was detected in para-cancerous tissues. The correlation between mutation and HCCs was significant （r = 0.72, P〈0.05）. （2）β-catenin gene exon 3 mRNA expression in 27 HCCs was higher than that in para-cancerous tissue （0.86±0.07 vs 0.33±0.04, P〈0.05）. （3） Acumulation of β-catenin protein in membrane, cytoplasms or nuclei was detected by immunohistochemistry in 59.2 % （16/27） of primary HCCs, while 11.1% （3/27） cases of para-cancerous tissues displayed weak membranous type positive staining. Conclusion β-catenin exon 3 mutations and its overexpression may play an important role in the hepatocellular carcinogenesis associated with HBV infection.

关 键 词：Β-链接素 癌 肝细胞 突变 肝细胞癌 基因突变 Β-CATENIN基因 逆转录-聚合酶链反应 异常表达 乙型肝炎病毒(HBV) 

分 类 号：R735.7[医药卫生—肿瘤] R739.63[医药卫生—临床医学]