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Epigenetic inactivation of the deleted in lung and esophageal cancer 1 gene in nasopharyngeal carcinoma
Author(s) -
Kwong Joseph,
Chow Lillian ShukNga,
Wong Albert YueHang,
Hung WingKi,
Chung Grace TinYun,
To KaFai,
Chan Franky L.,
Daigo Yataro,
Nakamura Yusuke,
Huang Dolly P.,
Lo KwokWai
Publication year - 2007
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20398
Subject(s) - nasopharyngeal carcinoma , cancer research , carcinogenesis , tumor suppressor gene , epigenetics , demethylating agent , dna methylation , gene silencing , lung cancer , biology , esophageal cancer , cancer , medicine , gene , pathology , gene expression , genetics , radiation therapy
Deletion of the short arm of chromosome 3 is a common event in nasopharyngeal carcinoma (NPC), suggesting that one or more tumor suppressor genes at 3p are involved in this cancer. DLEC1 , Deleted in Lung and Esophageal Cancer 1, located at 3p22.2, was recently identified as a candidate tumor suppressor gene in lung, esophageal, and renal cancers. In this study, we investigated the involvement of DLEC1 in the development of NPC. Down‐regulation of DLEC1 and promoter hypermethylation were observed in all NPC cell lines and xenografts but not in normal nasopharyngeal epithelial cells. Promoter hypermethylation of DLEC1 was also detected in 30 of 42 (71%) NPC primary tumors. Treatment of NPC cell lines with demethylating agent or histone deacetylase inhibitor resulted in restoration of DLEC1 expression. Overexpression of DLEC suppressed growth and reduced invasiveness of NPC cells. Furthermore, the tumorigenic potential of DLEC1 expressing NPC cells was highly reduced in nude mice. Taken together, our results strongly suggest that silencing of DLEC1 expression by promoter hypermethylation and histone deacetylation may be important in NPC tumorigenesis. © 2006 Wiley‐Liss, Inc.