In conclusion, although RNA integrity is lower in MIA and CA samples than in fresh frozen tissues, MIA and CA samples can be used to detect GAPDH PCR products up to 530 base pairs. This implies that tissue obtained by MIA yields a sufficient amount of RNA with a sufficient quality for gene array based research. Therefore, the MIA procedure is a feasible method for researchers to obtain metastatic tumor tissue for molecular translational research. Potential advantages of MIA over CA for obtaining metastatic tumor tissue are the higher chance of getting consent from bereaved relatives, and the better feasibility to reduce PMI, which is the most crucial factor for high quality post mortem tissue for molecular Wortmannin analyses. Constitutive active receptor was originally characterized as a drugactivated nuclear receptor that induces hepatic drug metabolism and secretion by activating genes that encode enzymes such as cytochrome P450s, sulfotransferases and UDP-glucuronosyltransferases as well as drug transporter genes. Subsequently, regulation by CAR has been extended far beyond drug metabolism to hepatic energy metabolism and cell growth and death, thereby becoming a critical factor in the development of diseases including diabetes and hepatocellular carcinoma. Therefore, understanding the molecular mechanism of CAR activation is essential for us to predict and control both beneficial and adverse effects caused by this activation. CAR is sequestered in its inactive form in the cytoplasm by phosphorylating its residue threonine 38; only non-phosphorylated CAR translocates into the nucleus, forms a heterodimer with RXR and activates target genes. Threonine 38 is phosphorylated when epidermal growth factor receptor signaling is stimulated, while repression of this signaling results in dephosphorylation that activates CAR. Consequently, CAR is, in principle, a cell signal-regulated nuclear receptor and this signal-mediated mechanism is now demonstrated in both mouse and human liver cells. As to regulation of CAR by therapeutic drugs, phenobarbital antagonizes EGFR signaling to dephosphorylate and activate CAR, while metformin represses CAR activation by preventing dephosphorylation. Thus, phosphorylation of threonine 38 is an essential factor that regulates CAR activation and nuclear translocation. In addition to this phosphorylation, we previously identified a tetratricopeptide repeat protein that interacts with CAR to regulate its cytoplasmic localization in HepG2 cells and named this TPR protein Cytoplasmic CAR Retention Protein. CCRP, also known as DNAJC7, is a member of the co-chaperone HSP40 family, which are structurally featured by J-domain and repeats of TPR motif, the 34-residue peptide forming a pair of anti-parallel a helices. The J-domain regulates ATP hydrolysis by HSP70, while the TPR motif mediates formation of homo-dimer or an array of hetero-complexes with nonTPR proteins via TPR motifs: co-chaperones with HSP90 and HSP70. In fact, CCRP formed a complex with CAR and HSP90, thereby causing accumulation of CAR in the cytoplasm of HepG2 cells.