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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2006-10-4
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pubmed:abstractText |
Deleted in colorectal cancer (DCC) is a candidate tumor-suppressor gene located at chromosome 18q21. However, DCC gene was found to have few somatic mutations and the heterozygous mice (DCC(+/-)) showed a similar frequency of tumor formation compared with the wild-type mice (DCC(+/+)). Recently, DCC came back to the spotlight as a better understating of its function and relationship with its ligand (netrin-1) had shown that DCC may act as a conditional tumor-suppressor gene. We evaluated hypermethylation as a mechanism for DCC inactivation in head and neck squamous cell carcinoma (HNSCC). DCC promoter region hypermethylation was found in 75% of primary HNSCC. There was a significant correlation between DCC promoter region hypermethylation and DCC expression (assessed by immunohistochemistry; P = 0.021). DCC nonexpressing HNSCC cell lines JHU-O12 and JHU-O19 with baseline hypermethylation of the DCC promoter were treated with 5-aza-2'-deoxycytidine (a demethylating agent) and reexpression of DCC was noted. Transfection of DCC into DCC-negative HNSCC cell lines resulted in complete abrogation of growth in all cell lines, whereas additional cotransfection of netrin-1 resulted in rescue of DCC-mediated growth inhibition. These results suggest that DCC is a putative conditional tumor-suppressor gene that is epigenetically inactivated by promoter hypermethylation in a majority of HNSCC.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1538-7445
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pubmed:author |
pubmed-author:BegumShahnazS,
pubmed-author:BraitMariana R OMR,
pubmed-author:CalifanoJoseph AJA,
pubmed-author:CarvalhoAndré LopesAL,
pubmed-author:ChuangAliceA,
pubmed-author:FazioVito MicheleVM,
pubmed-author:HenriqueRuiR,
pubmed-author:JerónimoCarmenC,
pubmed-author:JiangWei-WenWW,
pubmed-author:KochWayneW,
pubmed-author:LeeJunaJ,
pubmed-author:LiuChunyanC,
pubmed-author:MoonChul-soCS,
pubmed-author:NayakChetan SCS,
pubmed-author:ParkHannah LHL,
pubmed-author:PoetaLuanaL,
pubmed-author:RatovitskiEdwardE,
pubmed-author:SidranskyDavidD,
pubmed-author:TrinkBarryB,
pubmed-author:WestraWilliamW,
pubmed-author:ZhaoMingM,
pubmed-author:ZhouShaoyuS
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
66
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9401-7
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17018594-Carcinoma, Squamous Cell,
pubmed-meshheading:17018594-Cell Line, Tumor,
pubmed-meshheading:17018594-CpG Islands,
pubmed-meshheading:17018594-DNA, Neoplasm,
pubmed-meshheading:17018594-DNA Methylation,
pubmed-meshheading:17018594-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17018594-Genes, DCC,
pubmed-meshheading:17018594-Head and Neck Neoplasms,
pubmed-meshheading:17018594-Humans,
pubmed-meshheading:17018594-Loss of Heterozygosity,
pubmed-meshheading:17018594-Neoplasm Proteins,
pubmed-meshheading:17018594-Nerve Growth Factors,
pubmed-meshheading:17018594-Promoter Regions, Genetic,
pubmed-meshheading:17018594-Receptors, Cell Surface,
pubmed-meshheading:17018594-Transfection,
pubmed-meshheading:17018594-Tumor Suppressor Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Deleted in colorectal cancer is a putative conditional tumor-suppressor gene inactivated by promoter hypermethylation in head and neck squamous cell carcinoma.
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pubmed:affiliation |
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287-0910, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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