RRC ID 68532
Author Cheng YY, Yu J, Wong YP, Man EP, To KF, Jin VX, Li J, Tao Q, Sung JJ, Chan FK, Leung WK.
Title Frequent epigenetic inactivation of secreted frizzled-related protein 2 (SFRP2) by promoter methylation in human gastric cancer.
Journal 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.
Volume 97(7)
Pages 895-901
Published 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
Human and Animal Cells Kato III(RCB2088) MKN28(RCB1000) MKN45(RCB1001)