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.
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.
Authors: José Manuel González-Sancho; Oscar Aguilera; José Miguel García; Natalia Pendás-Franco; Cristina Peña; Santiago Cal; Antonio García de Herreros; Félix Bonilla; Alberto Muñoz Journal: Oncogene Date: 2005-02-03 Impact factor: 9.867
Authors: T Ishitani; J Ninomiya-Tsuji; S Nagai; M Nishita; M Meneghini; N Barker; M Waterman; B Bowerman; H Clevers; H Shibuya; K Matsumoto Journal: Nature Date: 1999-06-24 Impact factor: 49.962
Authors: O Aguilera; M F Fraga; E Ballestar; M F Paz; M Herranz; J Espada; J M García; A Muñoz; M Esteller; J M González-Sancho Journal: Oncogene Date: 2006-02-20 Impact factor: 9.867
Authors: Stefan Koch; Christopher T Capaldo; Stanislav Samarin; Porfirio Nava; Irmgard Neumaier; Arne Skerra; David B Sacks; Charles A Parkos; Asma Nusrat Journal: Mol Biol Cell Date: 2009-09-23 Impact factor: 4.138
Authors: H Zhang; C Yu; J Dai; J M Keller; A Hua; J L Sottnik; G Shelley; C L Hall; S I Park; Z Yao; J Zhang; L K McCauley; E T Keller Journal: Oncogene Date: 2013-06-10 Impact factor: 9.867