Abstract 929: Identification of ZBTB20 as a novel oncogene associated with the gender bias occurrence of hepatocellular carcinoma

The role of zinc finger and BTB domain containing 20 (ZBTB20) in hepatocellular carcinoma (HCC) is not well defined, as there are many discrepancies in the literature regarding its role in liver tumorigenesis. ZBTB20 has been implicated to play a role in liver cancer as a potential oncogene where increased expression is associated with poor survival. Conversely, it has been shown to be a transcriptional repressor of the alpha-fetoprotein (Afp) gene in adult liver using knockout studies, and reduced levels of ZBTB20 allow for upregulation of AFP with increased tumor severity in certain cases of HCC. Zbtb20 was initially identified as a candidate liver cancer gene in a forward genetic screen using the Sleeping Beauty (SB) insertional mutagenesis system in mice. In order to determine the role of ZBTB20 in liver cancer, the SB transposon system was used as a genetic tool to randomly integrate ZBTB20-expression vectors into the genome of fumarylacetoacetate hydrolase (Fah)-deficient mouse hepatocytes by hydrodynamic injection. This method of reverse genetics is a powerful tool for in vivo validation of novel oncogenes and tumor suppressor genes. Hepatocytes transgenic for ZBTB20 and in the context of tumor protein p53 (TP53) inactivation developed liver tumors in a male gender bias manner. Although ZBTB20 induced hepatic hypertrophy in both genders, hepatomegaly was observed exclusively in male animals. Interestingly, activation of the s-catenin (Ctnnb1) dependent Wnt signaling pathway was observed in all male experimental injected animals, indicating the role of Zbtb20 in this important pathway for liver tumorigenesis. Taken together, these results implicate the role of ZBTB20 as a novel oncogene involved in the gender bias occurrence of HCC. Citation Format: Vincent W. Keng, Barbara R. Tschida, Timothy P. Kuka, Branden S. Moriarity, Jason B. Bell, David A. Largaespada. Identification of ZBTB20 as a novel oncogene associated with the gender bias occurrence of hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 929. doi:10.1158/1538-7445.AM2014-929