1. Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer
- Author
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Tadateru Maehata, Hiroyuki Yamamoto, Nobuki Miyamoto, Yasushi Adachi, Chie Miyamoto, Noriyuki Akutsu, Hiroaki Taniguchi, Satoshi Yamaoka, Fumio Itoh, and Katsuhiko Nosho
- Subjects
animal structures ,Transcription, Genetic ,Receptors, Cell Surface ,Biology ,Transfection ,RNA interference ,Cell Line, Tumor ,Humans ,Gene silencing ,Gene family ,Neoplasm Invasiveness ,RNA, Messenger ,RNA, Small Interfering ,Promoter Regions, Genetic ,beta Catenin ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Gastrointestinal Neoplasms ,Regulation of gene expression ,Genetics ,Reverse Transcriptase Polymerase Chain Reaction ,Gastroenterology ,Wnt signaling pathway ,Membrane Proteins ,General Medicine ,Methylation ,DNA Methylation ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,body regions ,Gastric Cancer ,CpG site ,Tissue Array Analysis ,embryonic structures ,DNA methylation ,Cancer research ,Intercellular Signaling Peptides and Proteins ,CpG Islands ,RNA Interference ,Chemokines ,Signal Transduction - Abstract
To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer.We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR (MSP). Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and in vitro invasion assays after treatment with specific siRNA for those genes were performed.Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.
- Published
- 2008
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