DNA甲基化导致肝细胞癌SYK基因失表达  

Hypermethylation Leads to Silencing of SYK Gene in Hepatocellular Carcinoma

作　　者：元云飞[1] 汪建平[2] 李锦清[1] 王莉[3] 刘文姬[1] 崔伯康[1] 杨祖立[2] 张昌卿[4] 

机构地区：[1]中山大学肿瘤医院肝胆科华南肿瘤学重点实验室,广州市510060 [2]中山大学第一附属医院胃肠胰腺外科 [3]中山大学第一附属医院临床肿瘤学实验室 [4]中山大学第一附属医院肿瘤标本库

出　　处：《中国肿瘤临床》2006年第6期307-309,共3页Chinese Journal of Clinical Oncology

基　　金：CMB基金(编号:98-677);广东省科技厅基金(编号:2002B30107);广东省卫生厅基金(编号:A2002230);广东省教育厅基金资助(编号:Q-univ02009)

摘　　要：目的:探讨SYK(Spleentyrosinekinase,脾酪氨酸激酶)在肝细胞癌中的表达和不表达的机制。方法:分别用逆转录-聚合酶链反应(RT-PCR)方法和甲基化特异性聚合酶链反应(Methylation-specificPCR,MSP)检测SYK基因在肝癌细胞系(HepG2和Hep3B)和34例肝细胞癌组织、癌旁非瘤组织中的表达和甲基化情况。结果:肝癌细胞系Hep3B表达SYKmRNA,而HepG2不表达SYKmRNA。DNA甲基化转移酶抑制剂5-aza-2’-deoxycytidine处理HepG2后,SYK重新表达。Hep3B细胞SYK甲基化阴性,HepG2细胞SYK甲基化阳性。34例肝细胞癌组织标本中,5例SYKmRNA表达阴性,SYK基因甲基化均阳性;29例SYKmRNA表达阳性,其中3例SYK甲基化阳性,其余26例SYK甲基化阴性。肿瘤组织SYK基因的甲基化率为23.5%(8/34),而瘤旁肝组织中为8.8%(3/34)。结论:SYK基因启动子甲基化导致肝细胞癌SYKmRNA失表达,可能是肝癌发病的机制之一。Objective： To study the SYK （Spleen tyrosine kinase） expression and mechanism of its silencing in hepatocellular carcinoma （HCC）. Methods： RT-PCR （Reverse transcriptase-PCR） and MSP （Methylation-specific PCR） were used to check the expression and methylation status of SYK gene respectively, in HCC cell lines HepG2 and Hep3B and 34 paired samples of HCC tumor tissues and adjacent non-tumorous liver tissues. Results： SYK was expressed in Hep3B and was silenced in HepG2, and treatment of them with a DNA methyhransferase （DNMT） inhibitor reactivated the tran- scription of SYK in HepG2. SYK was methylated in HepG2 and unmethylated in Hep3B. In the tissues of primary tumor, the expression of SYK mRNA was negative in 5 cases and the SYK genes in all 5 cases were methylated. The expression of SYK mRNA was positive in 29 cases with SYK methylation in 3 cases and non SYK methylation in the other 26. Therefore, SYK gene was methylated in 23.5%（8/34） of the tumorous tissues of HCC. We also found that SYK was methylated in 8.8% （3/34） of the adjacent non-tumorous liver tissues. Conclusion： SYK is frequently silenced through an epigenetic pathway in HCC. The aberrant SYK methylation is responsible for the loss of expression and may consequently play a permissive role in hepatocarcinogenesis.

关 键 词：SYK 甲基化 肝细胞癌 

分 类 号：R735.7[医药卫生—肿瘤]