Ligand activation of peroxisome proliferator-activated receptor γ (PPARγ) has been reported to induce growth inhibition and apoptosis in various cancers including hepatocellular carcinoma (HCC). However, the effect of hepatitis B virus X protein (HBx) on PPARγ activation has not been characterized in hepatitis B virus (HBV)-associated HCC. Herein, we demonstrated that HBx counteracted growth inhibition caused by PPARγ ligand in HBx-associated HCC cells. We found that HBx bound to DNA binding domain of PPARγ and HBx/PPARγ interaction blocked nuclear localization and binding to recognition site of PPARγ. HBx significantly suppressed a PPARγ-mediated transactivation. These results suggest that HBx modulates PPARγ function through protein-protein interaction.
Bibliographical noteFunding Information:
We thank Drs. Ronald M. Evans, David J. Mangelsdof, and Heonjoong Kang for providing us with PPRE 3 -tk-LUC and pCMX-mPPARγ and Sankyo Co. Ltd for the troglitazone. This work was supported by a grant from the Korean National Cancer Control Program, Ministry of Health and Welfare, South Korea (02-1-2-0590).
- Hepatitis B virus X protein
- Peroxisome proliferator-activated receptor γ
- Protein-protein interaction