RRC ID 41883
著者 Leung WK, Yu J, Bai AH, Chan MW, Chan KK, To KF, Chan FK, Ng EK, Chung SC, Sung JJ.
タイトル Inactivation of helicase-like transcription factor by promoter hypermethylation in human gastric cancer.
ジャーナル Mol Carcinog
Abstract Helicase-like transcription factor (HLTF), a member of the SWI/SNF (mating type switching/sucrose nonfermenting) chromatin-remodeling complex, is recently found to be inactivated by promoter hypermethylation in human colorectal cancer. However, the role of this putative tumor suppressor gene in other tumors has not been determined. We evaluated the role of HLTF promoter hypermethylation in gastric cancer. Expression of HLTF was examined by reverse-transcription (RT)-polymerase chain reaction (PCR), and promoter hypermethylation in HLTF was determined by methylation-specific PCR. Bisulfite DNA sequencing was performed to determine the detailed methylation profiles of the promoter region. HLTF expression was lost in two of five gastric cell lines and in 13 (28%) of 46 primary gastric cancers. Accordingly, promoter hypermethylation was detected in the two cell lines and in nine of 13 gastric cancer samples. Of the ten normal gastric specimens and ten paired adjacent nonneoplastic tissues, methylation was detected in only one adjacent nonneoplastic tissue. Bisulfite DNA sequencing of the promoter region of HLTF showed that the CpG island was densely methylated in cell lines and cancer samples; this also appeared to correlate with expression level. Treatment of gastric cell lines that lacked HLTF expression with the demethylating agent 5-azacytidine (5-azaDC) restored HLTF expression. These results suggest that HLTF promoter hypermethylation is frequently demonstrated in human gastric cancer, and inactivation of HLTF or the chromatin-remodeling complex may play a crucial role in gastric carcinogenesis.
巻・号 37(2)
ページ 91-7
公開日 2003-6-1
DOI 10.1002/mc.10124
PMID 12766908
MeSH Adaptor Proteins, Signal Transducing Antimetabolites, Antineoplastic / pharmacology Azacitidine / pharmacology Carrier Proteins CpG Islands DNA Methylation* / drug effects DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Gastric Mucosa / cytology Gastric Mucosa / metabolism Gene Expression Regulation, Neoplastic Gene Silencing Humans MutL Protein Homolog 1 Neoplasm Proteins / genetics Neoplasm Proteins / metabolism Nuclear Proteins Promoter Regions, Genetic / drug effects Promoter Regions, Genetic / physiology* Sequence Analysis, DNA / methods Stomach Neoplasms / genetics* Stomach Neoplasms / metabolism Sulfites / chemistry Transcription Factors / genetics* Transcription Factors / metabolism Tumor Cells, Cultured
IF 3.825
引用数 20
WOS 分野 ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞