...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>World Journal of Gastroenterology >Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis.
【24h】

Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis.

机译：在食管鳞状肿瘤发生过程中，disabled-2表达的丧失是早期事件。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

AIM: Disabled-2 (DAB2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2 protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein. METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specific PCR. RESULTS: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (P(trend) < 0.001). Promoter hypermethylation of DAB2 was observed in 2 of 10 (20%) DAB2 immuno-negative ESCCs. CONCLUSION: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic gene silencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.
机译：目的：Disabled-2（DAB2）是在卵巢癌中鉴定的候选肿瘤抑制基因，对生长因子的促有丝分裂信号转导具有负面影响，并阻止ras活性。在最近的研究中，我们观察到了使用cDNA微阵列在ESCC中DAB2转录产物的下调。在本研究中，我们旨在确定DAB2蛋白缺失在食管肿瘤发生中的临床意义，并假设DAB2启动子高甲基化介导的基因沉默可能是该蛋白缺失的原因。方法：通过免疫组织化学分析DAB2在50例原发性食管鳞状细胞癌（ESCCs），30例明显增生，15例不典型增生和10例非恶性食管组织中的表达。为了确定启动子过度甲基化是否有助于ESCCs中DAB2表达的丧失，使用甲基化特异性PCR分析了DAB2免疫阴性肿瘤中DAB2启动子的甲基化状态。结果：在5/30（17％）增生，10/15（67％）不典型增生和34/50（68％）ESCC中观察到DAB2蛋白的丢失。从食管正常粘膜到增生，不典型增生和浸润性癌，DAB2蛋白明显减少（P（趋势）<0.001）。在10个（20％）DAB2免疫阴性ESCC中，有2个观察到了DAB2的启动子高甲基化。结论：DAB2蛋白表达的损失发生在食管癌发展的早期肿瘤形成早期，并持续沿着致癌途径。 ESCC中不常见的DAB2启动子甲基化表明表观遗传基因沉默只是导致ESCC中DAB2表达丧失的机制之一。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号