Enhanced cell survival of Hep3B cells by the hepatitis B x antigen effector, URG11, is associated with upregulation of beta-catenin.

Autor: Lian Z; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA., Liu J, Li L, Li X, Clayton M, Wu MC, Wang HY, Arbuthnot P, Kew M, Fan D, Feitelson MA
Jazyk: angličtina
Zdroj: Hepatology (Baltimore, Md.) [Hepatology] 2006 Mar; Vol. 43 (3), pp. 415-24.
DOI: 10.1002/hep.21053
Abstrakt: Intrahepatic expression of hepatitis B x antigen (HBxAg) is associated with the development of hepatocellular carcinoma (HCC), perhaps through trans-activation of selected cellular genes. When this was examined by PowerBlot analysis, upregulated levels of beta-catenin and several known beta-catenin effectors were observed in HBxAg-positive compared with HBxAg-negative HepG2 cells. When HBxAg was introduced into Hep3B cells, upregulated expression of wild-type beta-catenin was observed. This was also observed in Hep3B cells overexpressing the HBxAg upregulated gene, URG11. Upregulated expression of URG11 and beta-catenin correlated with HBxAg trans-activation function. Transient transfection assays with fragments of the beta-catenin promoter showed that it was activated by both HBxAg and URG11 and inhibited by URG11-specific small inhibitory RNA. The latter also inhibited the growth of Hep3BX cells in a serum-free medium, which correlated with depressed levels of beta-catenin. Activation of beta-catenin effector genes was observed in cells stably expressing HBxAg or overexpressing URG11 compared with control cells transfected with the pTOPFLASH reporter plasmid. Extensive costaining between HBxAg, URG11, and beta-catenin was observed in infected liver and HCC nodules, suggesting a close relationship in vivo. In conclusion, wild-type beta-catenin is activated by HBxAg, in part, through the upregulated expression of the HBxAg effector URG11. URG11 stimulates the beta-catenin promoter and hepatocellular growth and survival. These observations also suggest that URG11 may be a regulatory element in the beta-catenin signaling pathway and may be a target for chemoprevention of HCC.
Databáze: MEDLINE
Externí odkaz: