Modulation of E-cadherin expression by K-Ras: involvement of DNA methyltransferase-3b

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Title
Modulation of E-cadherin expression by K-Ras: involvement of DNA methyltransferase-3b
Author(s)
O Song Kwon; Sook-Jung Jeong; SunOk Kim; L He; Hee Gu Lee; K L Jang; H Osada; M Jung; Bo Yeon KimJong Seog Ahn
Bibliographic Citation
Carcinogenesis, vol. 31, no. 7, pp. 1194-1201
Publication Year
2010
Abstract
E-cadherin, as a tumor suppressor, plays an important role for intercellular adhesion involved in metastasis. Although K-Ras is highly expressed in a variety of cancers, the regulation of E-cadherin expression by K-Ras in association with DNA methylation and cell metastasis has not been completely clarified. In this study, E-cadherin expression was repressed in 267B1/K-Ras human epithelial prostate cancer cells stably overexpressing K-Ras, resulting from hypermethylation of E-cadherin promoter as evidenced by methylation-specific polymerase chain reaction (PCR), bisulfite sequencing, real-time reverse transcription-PCR and western blot analysis. The increased level of DNA methyltransferase (DNMT) 3b in 267B1/K-Ras cells was reduced by small interfering RNA-mediated knockdown of k-ras, whereas DNMT1 and DNMT3a did not change regardless of K-Ras or 5-aza-2′-deoxycytidine (5′-AzaC) treatment. Furthermore, binding of DNMT3b to E-cadherin promoter was increased in 267B1/K-Ras cells but was reduced by 5′-AzaC, as revealed by chromatin immunoprecipitation assay, which was in agreement with cell aggregation and invasive mobilization of the cells. Hence, our data suggest that increased binding of DNMT3b to E-cadherin promoter region by K-Ras cause promoter hypermethylation for reduced expression of E-cadherin, leading to the decreased cell aggregation and increased metastasis of human prostate cancer cells overexpressing K-Ras.
ISSN
0143-3334
Publisher
Oxford Univ Press
DOI
http://dx.doi.org/10.1093/carcin/bgq071
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
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