Document Detail


PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation.
MedLine Citation:
PMID:  17599052     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Array-based comparative genomic hybridization (array-CGH) has good potential for the high-throughput identification of genetic aberrations in cell genomes. In the course of a program to screen a panel of oral squamous-cell carcinoma (OSCC), cell lines for genomic copy-number aberrations by array-CGH using our in-house arrays, we identified a 3-Mb homozygous deletion at 10p12 in 1 of 18 cell lines (5.6%). Among seven genes located within this region, expression of PRTFDC1 mRNA was not detected in 50% (9/18) or decreased in 5.6% (1/18) of OSCC cell lines, but detected in normal oral epithelia and restored in gene-silenced OSCC cells without its homozygous loss after treatment with 5-aza-2'-deoxycytidine. Among 17 cell lines without a homozygous deletion, the hypermethylation of the PRTFDC1 CpG island, which showed promoter activity, was observed in all nine cell lines with no or reduced PRTFDC1 expression (52.9%). Methylation of this CpG island was also observed in primary OSCC tissues (8/47, 17.0%). In addition, restoration of PRTFDC1 in OSCC cells lacking its expression inhibited cell growth in colony-formation assays, whereas knockdown of PRTFDC1 expression in OSCC cells expressing the gene promoted cell growth. These results suggest that epigenetic silencing of PRTFDC1 by hypermethylation of the CpG island leads to a loss of PRTFDC1 function, which might be involved in squamous cell oral carcinogenesis.
Authors:
E Suzuki; I Imoto; A Pimkhaokham; T Nakagawa; N Kamata; K-I Kozaki; T Amagasa; J Inazawa
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-18
Journal Detail:
Title:  Oncogene     Volume:  26     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-13     Completed Date:  2008-01-03     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  7921-32     Citation Subset:  IM    
Affiliation:
Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Azacitidine / analogs & derivatives,  pharmacology
Carcinoma, Squamous Cell / genetics*,  pathology
Cell Line, Tumor
Cell Proliferation
Chromosomes, Human, Pair 10
CpG Islands
DNA Methylation*
Gene Silencing*
Genes, Tumor Suppressor*
Humans
Mouth Neoplasms / genetics*,  pathology
Nucleic Acid Hybridization
Promoter Regions, Genetic*
RNA, Messenger / analysis
Chemical
Reg. No./Substance:
0/RNA, Messenger; 320-67-2/Azacitidine; 776B62CQ27/decitabine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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