Abstract 1245: Hepatitis B virus X protein induces Src homology 2-containing protein tyrosine phosphatase, SHP2, expression through the NF-kB pathway in HBV-infected hepatocellular carcinomas

Abstract

Abstract Hepatitis B virus X protein (HBx) has a crucial role in the development of hepatocellular carcinoma and activates many transcription factors, including AP-1, NF-kB and CREB. In the present study, we showed that increased SHP2 expression was observed in 16 (53%) of the 30 cases of HBV-positive hepatocellular carcinomas tissues. We investigated the relationship of SHP2 and HBx in stably HBx-overexpressing Huh7-X and transiently HBx expressing HEK293 cells. The level of SHP2 proteins was concomitantly increased with HBX in a dose-dependent manner in HEK293 cells. We identified a putative NF-kB binding site within 500 bp of the SHP2 promoter and also observed the decrease of SHP2 proteins after the treatment of the NF-kB/p65 inhibitor, parthenolide in HBx expressing cell. In addition, we confirmed that the complex of NF-kB and HBx proteins direct bound to the SHP2 promoter by chromatin immunoprecipitation (ChIP)-real time PCR assays. Taken together, we conclude that HBV infection induces SHP2 overexpression through the HBx-NF-kB pathway. Currently, we are investigating the effects of SHP2 overexpression in the proliferation of hepatocellular carcinoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1245. doi:1538-7445.AM2012-1245