癌变·畸变·突变2011，Vol.23Issue(4)：269-274,6.DOI:10.3969/j.issn.1004-616x.2011.04.006
贲门腺癌中Smad4基因甲基化状态分析
CpG island methylation of Smad4 gene in gastric cardia adenocarcinoma
摘要
Abstract
OBJECTIVE: We investigated the promoter and exonl melhylation of mothers against decapentaplegic homolog 4 (Smad4) and its correlation with protein expression of TGF- β1 in gastric cardia adenocarcinoma (GCA). METHODS: Methylation-specific PCR approach, RT-PCR and immunohislochemistry methods were used to examine the methylation status of the 5' CpC island, mRNA and protein expression of Smad4. Immunohistochemistry method was used to detect the protein expression of TGF-β1 in tumors and corresponding normal tissues. RESULTS: For the promoter site, Smad4 was methylated in 6/110 (5.5%) tumor specimens. For the 5' UTR of exonl, Smad4 was methylated in 24.5% (27/110) tumor specimens. Both were significantly higher than that in corresponding normal tissues (P<0.05). Methylation frequency of Smad4 in the 5' UTR of exonl was significantly higher than that in the promoter site (P<0.01). Smad4 mRNA and protein expression of tumor tissues were significantly lower than that in corresponding normal tissues and was inversely correlated with its methylation status. Seventy-two of 110 (65.5%) tumor tisssues demonstrated positive immunostaining for TGF- β1 and the frequency of positive TGF- β1 protein expression was significantly higher than that in corresponding normal tissues (P<0.01). The protein expressions of TGF-β1 were significantly different among various stages and differentiations of GCA (P<0.05). The protein expression of Smad4 was inversely correlated with TCF- β1 in GCA. CONCLUSION: Hypermethylation of Smad4 in 5' UTR of exonl and the higher protein expression of TGF- β1 may play important roles in the development of gastric cardia adenocarcinoma.关键词
贲门腺癌；DNA甲基化；Smad4；TGF-β1Key words
gastric cardia adenocarcinoma/DNA methylation/Smad4 gene/TGF-β1 gene分类
医药卫生引用本文复制引用
郭炜,董稚明,郭艳丽,杨植彬,邝钢..贲门腺癌中Smad4基因甲基化状态分析[J].癌变·畸变·突变,2011,23(4):269-274,6.基金项目
河北省医学科学研究重点课题计划(20090465) （20090465）
