We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1.
- Authors
Jung-Ok Lee; Hyun Jin Kwun; Jin Kyu Jung; Kyung Hee Choi; Do Sik Min; Kyung Lib Jang
- Abstract
E-cadherin is a key cell adhesion molecule implicated as a tumor suppressor, which is frequently altered in hepatocellular carcinoma, especially in hepatitis B virus (HBV)- related tumors. Here, we report that HBV X protein (HBx) represses E-cadherin expression at the transcription level. Based on the differential effects of HBx natural variants, we determined that Lys-130 in the transactivation domain of HBx is critical for the E-cadherin repression. The repression effect of HBx was abolished after treatment with DNA methyltransferase inhibitor, 5' -Aza-2'dC. In addition, methylation-specific PCR analysis revealed that the CpG island 1 of E-cadherin promoter is hypermethylated by HBx. Furthermore, HBx induces DNA methyltransferase 1 expression by stimulating its transcription. Therefore, we conclude that HBx represses E-cadherin expression by inducing methylation-mediated promoter inactivation. The reduced E-cadherin expression results in dramatic morphological changes of the HBx-expressing cells. In addition, HBx-expressing cells aggregate poorly in suspension culture, reflecting their altered intercellular interactions. The biological significance was further demonstrated by the increased collagen invasion ability of HBx-expressing cells. Therefore, the present study suggests that HBx plays a role during hepatocellular carcinogenesis by favoring cell detachment from the surrounding cells and migration outside of the primary tumor site.
- Publication
Oncogene, 2005, Vol 24, Issue 44, p6617
- ISSN
0950-9232
- Publication type
Academic Journal
- DOI
10.1038/sj.onc.1208827