%0 Journal Article
%T Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer
%A Tadateru Maehata
%A Hiroaki Taniguchi
%A Hiroyuki Yamamoto
%A Katsuhiko Nosho
%A Yasushi Adachi
%A Nobuki Miyamoto
%A Chie Miyamoto
%A Noriyuki Akutsu
%A Satoshi Yamaoka
%A Fumio Itoh
%J World Journal of Gastroenterology
%D 2008
%I Baishideng Publishing Group Co. Limited
%X AIM: To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer.METHODS: 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.RESULTS: 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.CONCLUSION: Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.
%K Dickkopf genes
%K Kremen2 gene
%K Methylation
%K Wnt signaling
%K Gastrointestinal cancer
%U http://www.wjgnet.com/1007-9327/full/v14/i17/2702.htm