title: Decreased expression and aberrant hypermethylation of the SFRP genes in human gastric cancer.
abstract: OBJECTIVE
  Expression of secreted frizzled-related protein (SFRP) genes is silenced by aberrant methylation of the promoter region in several cancers. SFRP genes have recently been mapped on chromosome 8p12-p12.1 (SFRP1), 4q31.3 (SFRP2) and 10q24.1 (SFRP5), respectively. Interestingly, the SFRP family genes are located where the frequent LOH have been shown in gastric cancer samples.
  
  
  METHODS
  Methylation status and expression of SFRP genes were investigated in gastric cancer cell lines and surgically resected specimens.
  
  
  RESULTS
  A significant decrease in the expression of SFRP1 and SFRP5 was observed in gastric cancer compared with corresponding normal gastric tissues. The SFRP1 gene was hypermethylated in all 35 cancer tissues and corresponding non-cancerous tissues, as well as all seven gastric cancer cell lines, whereas SFRP2 gene was methylated in 83% of cancer tissues and 69% of normal epithelium, and SFRP5 in 43% and 54% of the same groups, respectively. Although gender, age, tumor size, pathological type, depth of tumor and TNM stage were not significantly correlated with the expression of SFRP genes, a significant decrease in the SFRP1 expression score was observed among gastric cancer with lymph node metastasis.
  
  
  CONCLUSIONS
  These results indicate the possibility that SFRP1 and 5 genes function as tumor suppressors, the down-regulation of which not only contributes to carcinogenesis but is also associated to some extent with the metastatic potential of cancer cells.
authors.affiliation: Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D019175:DNA Methylation; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C109618:SFRP2 protein, human; C118511:SFRP5 protein, human