title: Frequent silencing of protocadherin 8 by promoter methylation, a candidate             tumor suppressor for human gastric cancer.
abstract: The cadherins are a family of cell surface glycoproteins responsible for             cell adhesion which play an important role in cell morphology, contact inhibition             and signal transduction during tumorigenesis. Protocadherin 8 (PCDH8), a member             of the cadherin family, has been reported to act as a tumor suppressor involved             in oncogenesis in breast cancer. In this study, we aimed to investigate the epigenetic             inactivation of PCDH8 and its tumor suppressor function in gastric cancer. The             expression of PCDH8 was markedly reduced or silenced in gastric cancer cell lines             compared with normal gastric cells or tissues. Methylation of the PCDH8 gene promoter             was observed in 100% (4/4) of cell lines and 55.38% (36/65) of the primary gastric             cancer by methylation-specific PCR, but not in normal gastric mucosa (0/10). Methylated             PCDH8 was significantly associated with lymph node metastasis in a logistic regression             analysis. The demethylation reagent 5-aza-2'-deoxycytidine was able to restore             or upregulate PCDH8 expression in gastric cancer cell lines. Ectopic expression             of PCDH8 in silenced gastric cancer cells significantly inhibited cell migration             and induced apoptosis. For the first time, our study demonstrates the epigenetic             inactivation of PCDH8 by promoter methylation and its tumor suppressor function             in human gastric cancer. Thus, PCDH8 could be identified as a candidate tumor             suppressor in human gastric cancer.
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College of Xi'an JiaoTong University, Xi'an 710061, PR China.
authors.forename: Danjie
authors.initials: D
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liao
authors.forename: Tieqiang
authors.initials: T
authors.lastname: Bi
authors.forename: Haijun
authors.initials: H
authors.lastname: Li
authors.forename: Xiangming
authors.initials: X
authors.lastname: Che
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019175:DNA Methylation / Q000235:genetics*; D000077209:Decitabine; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000091363:Protocadherins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015820:Cadherins; C115816:PCDH8 protein, human; D000091363:Protocadherins; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine