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
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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 |
|