Epigenetic silencing of somatostatin in gastric cancer.
Epigenetic silencing of somatostatin in gastric cancer.
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DOI：
10.1007/s10620-010-1422-z
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发表时间：
2011-01
影响因子：
3.1
通讯作者：
El-Rifai, Wael
中科院分区：
文献类型：
--
作者：
Jackson, Kaya;Soutto, Mohammed;Peng, DunFa;Hu, TianLing;Marshal, Dana;El-Rifai, Wael
生长抑素（SST）是胃泌素刺激胃酸分泌的主要抑制剂，在几种人类癌症中具有有效的抗肿瘤和抗分泌活性。本研究旨在探讨SST基因在胃腺癌中的表达水平及其可能的表观遗传调控机制。应用实时荧光定量rt - PCR和亚硫酸氢盐焦磷酸测序技术对原发性胃癌组织样本和细胞系进行研究。实时定量RT-PCR分析显示，93%的胃癌样本（30/32）与21个正常样本相比，SST转录物下调（P<0.001）。由于在SST启动子中存在一个大的CpG岛，我们接下来使用定量亚硫酸盐焦磷酸测序技术检测了其启动子DNA甲基化水平。结果表明，与正常样本相比，肿瘤样本中SST启动子DNA甲基化水平显著增加（P<0.05）。在7个胃癌细胞系中也检测到启动子DNA的超甲基化和SST的沉默。为了证实启动子DNA甲基化作为调控SST表达的表观遗传机制的作用，我们用5- aza -脱氧胞苷处理AGS胃癌细胞。这种处理导致SST启动子DNA甲基化水平降低，同时恢复其mRNA表达。我们的研究结果表明，启动子DNA甲基化水平在胃癌中调控SST表达中起关键作用。这一发现为进一步研究SST在胃癌发生中的作用及其作为胃癌生物标志物的潜力奠定了基础。
Somatostatin (SST), a primary inhibitor of gastrin-stimulated gastric acid secretion, has potent antitumor and anti-secretory activities in several human cancers. This study was performed to investigate the SST gene expression levels and possible epigenetic mechanisms that regulate its expression in gastric adenocarcinomas. Quantitative real time-RT PCR and quantitative bisulfite pyrosequencing technologies were applied to study primary gastric cancer tissue samples and cell lines. Quantitative real-time RT-PCR analysis demonstrated down-regulation of SST transcript in 93% of gastric carcinoma samples (30/32), as compared to 21 normal samples (P<0.001). Because of the presence of a large CpG island in the SST promoter, we next examined its promoter DNA methylation levels using quantitative bisulfite pyrosequencing technology. The results demonstrated a significant increase in SST promoter DNA methylation levels in tumor samples as compared to normal samples (P<0.05). Promoter DNA hypermethylation and silencing of SST was also detected in seven gastric cancer cell lines that we tested. To confirm the role of promoter DNA methylation as an epigenetic mechanism regulating SST expression, AGS gastric cancer cells were treated with 5-Aza-deoxycytidine. This treatment led to reduction in the promoter DNA methylation levels of SST accompanied by restoration of its mRNA expression. Our results indicate that promoter DNA methylation levels play a critical role in regulating SST expression in gastric cancer. This finding provides a foundation for further studies on the role of SST in gastric carcinogenesis and its potential as a biomarker for gastric cancers.
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影响因子：
8
作者：
Clement, G.;Braunschweig, R.;Benhattar, J.
通讯作者：
Benhattar, J.
影响因子：
4.8
作者：
Lee, OJ;Schneider-Stock, R;El-Rifai, W
通讯作者：
El-Rifai, W
影响因子：
30.8
作者：
Cameron, EE;Bachman, KE;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
24.5
作者：
Peng DF;Razvi M;Chen H;Washington K;Roessner A;Schneider-Stock R;El-Rifai W
通讯作者：
El-Rifai W
DOI：
10.1111/j.1749-6632.2003.tb05976.x
发表时间：
2003-01-01
期刊：
EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT
影响因子：
--
作者：
Jones, PA
通讯作者：
Jones, PA