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

作　　者：Kumar Anupam Chatopadhyay Tusharkant Siddhartha Datta Gupta Ralhan Ranju 

机构地区：[1]Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India [2]Department of GI Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India [3]Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India

出　　处：《World Journal of Gastroenterology》2006年第37期6041-6045,共5页世界胃肠病学杂志（英文版）

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-specifi c 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 (Ptrend < 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 genesilencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.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 （Ptrend 〈 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.

关 键 词：Disabled-2 DOC-2 Esophageal cancer Promoter hypermethylation DYSPLASIA 

分 类 号：R735.1[医药卫生—肿瘤]