Pregnane X receptor regulates the expression of many genes involved in xenobiotic metabolism. Its target genes include CYP3A4, CYP2B6, CYP2C subfamily, several conjugation enzymes and drug transporters as well. Therefore, cell lines were treated with PXR agonists or transfected with PXR expression vector to increase expression of several CYP mRNAs. The potential advantage here is that several PXR-target genes may be up-regulated at the same time only by introducing the sole PXR construct. However, the consequence of transactivation of PXR has often been moderate in various reporter gene assays and the up-regulation of endogenous CYP3A4 or CYP2B6 mRNAs has been quite modest. These findings indicated the limitation of transcriptionally regulating CYP genes by introducing a native PXR into hepatoma cell lines. Inspired by the function-modular structure of PXR, some studies tried to append PXR molecule with an extra heterogeneous strong AD, with expectation to U0126 enhance the trans-activation mediated by PXR. For example, transgenic mice were generated carrying fusion of the hPXR cDNA with the AD from the herpes simplex viral protein 16, which had been used to form an ecdysone-inducible regulator for gene therapy and cell biological studies. Due to the constitutive activity of VP16-AD fusion partner, these transgenic mice showed up-regulation of PXR-target hepatic genes without any exposure to PXR ligand. Similarly, the AD of p65 subunit of nuclear factor kB has been applied to form a nuclear receptor-based regulator for in vitro cell model for drug and xenobiotic metabolism. Based on these previous reports, we proposed that trans-activation effect of hPXR may be enhanced by fusion with a heterologous AD, and subsequently, the ability of these ����chimeric hPXR���� to activate CYP3A4 gene in hepatoma cells would be higher as compared to native hPXR; thus, chimeric hPXRs might be effective in producing hepatoma cells with an increased expression of CYP3A4. In our study, C3A cell line, a clonal derivative of hepatoblastoma- based HepG2, was CP-690550 employed as cell model due to its relatively higher-level of remnant hepatic phenotype and popularity in drug testing.