Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer |
| |
Authors: | Maehata Tadateru Taniguchi Hiroaki Yamamoto Hiroyuki Nosho Katsuhiko Adachi Yasushi Miyamoto Nobuki Miyamoto Chie Akutsu Noriyuki Yamaoka Satoshi Itoh Fumio |
| |
Affiliation: | 1. Department of Gastroenterology and Hepatology,St.Marianna University School of Medicine,Kanagawa 216-8511,Japan 2. First Department of Internal Medicine,Sapporo Medical University,Sapporo 060-8543,Japan |
| |
Abstract: | 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. |
| |
Keywords: | Dickkopf genes Kremen2 gene Methylation Wnt signaling Gastrointestinal cancer |
本文献已被 维普 万方数据 PubMed 等数据库收录! |