Epigenetic inactivation of the deleted in lung and esophageal cancer 1 gene in nasopharyngeal carcinoma.
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.
Kwong
Joseph
J
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
Chow
Lillian Shuk-Nga
LS
Wong
Albert Yue-Hang
AY
Hung
Wing-Ki
WK
Chung
Grace Tin-Yun
GT
To
Ka-Fai
KF
Chan
Franky L
FL
Daigo
Yataro
Y
Nakamura
Yusuke
Y
Huang
Dolly P
DP
Lo
Kwok-Wai
KW
D000328:Adult; D000368:Aged; D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*
C119064:DLEC1 protein, human; D006657:Histones; D025521:Tumor Suppressor Proteins