title: Aberrant up-regulation of LAMB3 and LAMC2 by promoter demethylation in gastric cancer.
abstract: The LAMB3 and LAMC2 genes encode the laminin-5 β3 and γ2 chains, respectively, which are parts of laminin-5, one of the major components of the basement membrane zone. Here, we report the frequent up-regulation of LAMB3 and LAMC2 by promoter demethylation in gastric cancer. Gene expression data analysis showed that LAMB3 and LAMC2 were up-regulated in various tumor tissues. Combined analyses of DNA methylation and gene expression of both genes in gastric cancer cell lines and tissues showed that DNA hypomethylation was associated with the up-regulation of both genes. Treatment with a methylation inhibitor induced LAMB3 and LAMC2 expression in gastric cancer cell lines in which both genes were silenced. By chromatin immunoprecipitation assay, we showed the activation histone mark H3K4me3 was associated with the expression of both genes. The expression level of LAMB3 affected multiple malignant phenotypes in gastric cancer cell lines. These results suggest that epigenetic activation of LAMB3 and LAMC2 may play an important role in gastric carcinogenesis.
authors.affiliation: Medical Genomics Research Center, University of Science and Technology, KRIBB, and Daejeon 305-806, Republic of Korea.
authors.forename: Oh-Hyung
authors.initials: OH
authors.lastname: Kwon
authors.forename: Jong-Lyul
authors.initials: JL
authors.lastname: Park
authors.forename: Mirang
authors.initials: M
authors.lastname: Kim
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Han-Chul
authors.initials: HC
authors.lastname: Lee
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Seung-Moo
authors.initials: SM
authors.lastname: Noh
authors.forename: Kyu-Sang
authors.initials: KS
authors.lastname: Song
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Yoo
authors.forename: Sang-Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D007797:Laminin; D000097794:Kalinin; C400567:LAMC2 protein, human