| RRC ID |
68532
|
| 著者 |
Cheng YY, Yu J, Wong YP, Man EP, To KF, Jin VX, Li J, Tao Q, Sung JJ, Chan FK, Leung WK.
|
| タイトル |
Frequent epigenetic inactivation of secreted frizzled-related protein 2 (SFRP2) by promoter methylation in human gastric cancer.
|
| ジャーナル |
Br J Cancer
|
| Abstract |
The role of secreted frizzled-related protein (SFRP) genes in gastric cancer remains largely unknown. We determined the frequency and functional significance of SFRPs hypermethylation in human gastric cancer. The expression and methylation status of four SFRP members (SFRP1, 2, 4, and 5) in primary gastric cancer samples was screened. The biological effects of SFRP were analysed by flow cytometry, cell viability assay and in vivo tumour growth in nude mice. Among the four SFRPs, only SFRP2 was significantly downregulated in gastric cancer as compared to adjacent non-cancer samples (P<0.01). Promoter hypermethylation of SFRP2 was detected in 73.3% primary gastric cancer tissues, 37.5% of samples showing intestinal metaplasia and 20% adjacent normal gastric tissues. Bisulphite DNA sequencing confirmed the densely methylated SFRP2 promoter region. Demethylation treatment restored the expression of SFRP2 in gastric cancer cell lines. Forced expression of SFRP2 induced cell apoptosis, inhibited proliferation of gastric cancer cells and suppressed tumour growth in vivo. Moreover, methylated SFRP2 was detected in 66.7% of serum samples from cancer patients but not in normal controls. In conclusion, epigenetic inactivation of SFRP2 is a common and early event contributing to gastric carcinogenesis and may be a potential biomarker for gastric cancer.
|
| 巻・号 |
97(7)
|
| ページ |
895-901
|
| 公開日 |
2007-10-8
|
| DOI |
10.1038/sj.bjc.6603968
|
| PII |
6603968
|
| PMID |
17848950
|
| PMC |
PMC2360406
|
| MeSH |
Adaptor Proteins, Signal Transducing
Adenocarcinoma / genetics
Adenocarcinoma / metabolism
Animals
Apoptosis
Azacitidine
Cell Line, Tumor
Cell Proliferation
DNA Methylation*
DNA Primers / chemistry
Epigenesis, Genetic*
Eye Proteins / genetics
Eye Proteins / metabolism
Flow Cytometry
Gene Expression Regulation, Neoplastic*
Gene Silencing
Humans
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Mice
Mice, Nude
Promoter Regions, Genetic*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Stomach Neoplasms / genetics*
Stomach Neoplasms / metabolism
|
| IF |
5.791
|
| リソース情報 |
| ヒト・動物細胞 |
Kato III(RCB2088)
MKN28(RCB1000)
MKN45(RCB1001) |
