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한국생명공학연구원

Biochem. Biophys. Res. Commun., Mar 25 2011, 406 (4) | https://doi.org/10.1016/j.bbrc.2011.02.082 Aberrant up-regulation of LAMB3 and LAMC2 by promoter demethylation in gastric cancer

Oh-Hyung Kwon ^{a c}, Jong-Lyul Park ^{a b}, Mirang Kim ^a, Jeong-Hwan Kim ^a, Han-Chul Lee ^a, Hee-Jin Kim ^{a b}, Seung-Moo Noh ^d, Kyu-Sang Song ^e, Hyang-Sook Yoo ^a, Sang-Gi Paik ^c, Seon-Young Kim ^{a b *}, Yong Sung Kim ^{a b *}

^aMedical Genomics Research Center, University of Science and Technology, KRIBB, and Daejeon 305-806, Republic of Korea
^bDepartment of Functional Genomics, University of Science and Technology, KRIBB, and Daejeon 305-806, Republic of Korea
^cDepartment of Biological Science, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea
^dDepartment of General Surgery, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea
^eDepartment of Pathology, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea

^*Corresponding authors: correspondence to Seon-Young Kim or Yong Sung Kim

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.

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