Linked Life Data

21373750

Source:http://linkedlifedata.com/resource/pubmed/id/21373750

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-3-22
pubmed:abstractText
CDH1, a cell adhesion molecule, which plays a key role in maintaining the epithelial phenotype, is regarded as an invasion-suppressor gene in light of accumulating evidence from in vitro experiments and clinical observations. In an attempt to clarify the mechanism responsible for inactivation of this gene in carcinomas, we investigated the methylation status of the CDH1 gene 5'-CpG islands and its regulatory mechanism in the progression of esophageal squamous cell carcinoma. Real-time methylation-specific polymerase chain reaction (qMSP) and treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR) were conducted to analyze the methylation status at the CDH1 promoter region in the human esophageal carcinoma cell lines, EC1 and EC9706. A total of 235 invasive esophageal squamous cell carcinomas (ESCC) at stages I-IV and their corresponding normal tissue samples, were included in an immunohistochemistry study and methylation analysis of CDH1. The results demonstrate that in EC1 and EC9706 cells, the CDH1 promoter is methylated and treatment with 5-Aza-CdR restored CDH1 expression. Enhanced CDH1 expression decreased cell migration, invasion ability and increased adhesion ability. Decreased CDH1 expression was detected in 59.6% of ESCC tissues, compared with their adjacent non-neoplastic epithelia, which had a close correlation with the primary tumor status, lymph node status, distant metatasis and clinicopathologic stage. Hypermethylation at the CDH1 promoter was detected in 97.9% of 140 cases of ESCC with low CDH1 expression. The methylation of CDH1 promoters (P=0.929) was closely correlated with the lack of expression of their corresponding proteins. The Cox regression model for survival analysis showed that increases in CDH1 methylation had a greater impact on the prognosis than tumor clinical stage. These findings suggest that CDH1 gene silencing by promoter hypermethylation and the resultant reduction of CDH1 expression may play an important role in the progression of ESCC. CDH1 methylation was a significant predictor of survival in ESCC patients after surgery.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1791-244X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
625-35
pubmed:meshHeading
pubmed-meshheading:21373750-Adult, pubmed-meshheading:21373750-Aged, pubmed-meshheading:21373750-Aged, 80 and over, pubmed-meshheading:21373750-Azacitidine, pubmed-meshheading:21373750-Cadherins, pubmed-meshheading:21373750-Carcinoma, Squamous Cell, pubmed-meshheading:21373750-Cell Adhesion, pubmed-meshheading:21373750-Cell Cycle, pubmed-meshheading:21373750-Cell Line, Tumor, pubmed-meshheading:21373750-Cell Movement, pubmed-meshheading:21373750-Cell Shape, pubmed-meshheading:21373750-Cell Survival, pubmed-meshheading:21373750-DNA Methylation, pubmed-meshheading:21373750-DNA Modification Methylases, pubmed-meshheading:21373750-Down-Regulation, pubmed-meshheading:21373750-Esophageal Neoplasms, pubmed-meshheading:21373750-Female, pubmed-meshheading:21373750-Humans, pubmed-meshheading:21373750-Male, pubmed-meshheading:21373750-Methylation, pubmed-meshheading:21373750-Middle Aged, pubmed-meshheading:21373750-Neoplasm Invasiveness, pubmed-meshheading:21373750-Neoplasm Staging, pubmed-meshheading:21373750-Promoter Regions, Genetic, pubmed-meshheading:21373750-Transcription, Genetic
pubmed:year
2011
pubmed:articleTitle
Hypermethylation-modulated down-regulation of CDH1 expression contributes to the progression of esophageal cancer.
pubmed:affiliation
Zhejiang Cancer Research Institute, Hangzhou 310022, PR China. lingzq@hotmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't