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Kwon O.,Korea Research Institute Yangcheong Ri | Jeong S.J.,Korea Research Institute Yangcheong Ri | Kim S.O.,Korea Research Institute Yangcheong Ri | He L.,Korea Research Institute Yangcheong Ri | And 6 more authors.
Carcinogenesis | Year: 2010

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. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org. Source

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