title: Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer.
abstract: By allelotyping for loss of heterozygosity (LOH), we previously identified a deletion region that harbors the candidate tumor suppressor gene DAL-1 at 18p11.3 in sporadic gastric cancers (GCs). The expression and function of DAL-1 in GCs remained unclear. Here, we demonstrated that the absence of or notable decreases in the expression of DAL-1 mRNA and protein was highly correlated with CpG hypermethylation of the DAL-1 promoter in primary GC tissues and in GC cell lines. Furthermore, abnormal DAL-1 subcellular localization was also observed in GC cells. Exogenous DAL-1 effectively inhibited cancer cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT); exogenous DAL-1 also promoted apoptosis in GC AGS cells. When endogenous DAL-1 was knocked down in GC HGC-27 cells, the cells appeared highly aggressive. Taken together, these findings provide solid evidence that aberrant expression of DAL-1 by hypermethylation in the promoter region results in tumor suppressor gene behavior that plays important roles in the malignancy of GCs. Understanding the role of it played in the molecular pathogenesis of GC, DAL-1 might be a potential biomarker for molecular diagnosis and evaluation of the GC.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Scientific Research Centre, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Man
authors.initials: M
authors.lastname: Xu
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cui
authors.affiliation: Computer teaching and research section, School of Basic Medical Science, Harbin Medical University, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Scientific Research Centre, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Scientific Research Centre, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.affiliation: Scientific Research Centre, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Dexu
authors.initials: D
authors.lastname: Wang
authors.affiliation: Scientific Research Centre, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Jingcui
authors.initials: J
authors.lastname: Yu
mesh_terms: D045744:Cell Line, Tumor; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C116887:EPB41L3 protein, human; D008840:Microfilament Proteins; D025521:Tumor Suppressor Proteins