The leading cause of human hepatocellular carcino-been observed in hepatocellular carcinomas (HCCs), mas (HCCs) is hepatitis B virus (HBV) infection. Woodmaking the prognosis for patients with HCC very poor. 6 chucks infected with a closely related hepadnavirus, HCC is one of the most common cancers in the world 7 ; woodchuck hepatitis virus (WHV), serve as a model for therefore, it is important to understand the mecha-HBV because woodchucks chronically infected with nisms of drug resistance in hopes of developing better WHV also develop hepatocellular carcinomas. Increased therapeutic modalities in the treatment of HCC.
expression of p-glycoprotein (pgp) in human HCCs is
The overexpression of MDR genes that code for a pa common obstacle in successful cancer chemotherapy. glycoprotein (pgp) has been shown to correlate with Pgps are encoded by a family of multidrug-resistance levels of drug resistance in both cell culture 8 and hu-(MDR) genes. Livers from uninfected and WHV-infected man liver biopsy samples. 9,10 In normal hepatocytes, woodchucks were examined to determine if pgp was expressed in HCCs and if there was a difference in expres-pgp functions as a secretory pump that provides a prosion between HCCs and nonneoplastic liver. A 170-kd tective mechanism against cytotoxic plant alkaloids, protein was identified by Western blot in HCCs, dietary xenobiotics, 11 and chemical carcinogens such as whereas, constitutive pgp was not detected in normal benzo(a)pyrene 12 and possibly 2-amino-acetylfluoliver taken from the same animals in 3 of 3 cases. Immurene. 13 There is a second class of pgp found in human nolocalization of the pgp with a panel of monoclonal liver that is encoded by MDR2, the function of which antibodies revealed intensification of staining in 7 of 20 has not been determined. The mouse homolog, mdr2, foci and 12 of 22 HCCs from six animals. Using primers has been shown to be involved in lipid trafficking. 14 In for the human MDR1 gene, a single product was detected mice and rats, there are three MDR genes, mdr1, mdr2, by reverse-transcribed polymerase chain reaction (RTand mdr3, but only mdr1 and mdr3 appear to partici-PCR) from HCCs. We have shown an increase in pgp in HCCs compared with normal liver from WHV-infected pate in drug resistance. 15,16 woodchucks. This is the first example of the induction Abbreviations: MDR, multidrug resistance; HCC, hepatocellular carcinovirus, (2) the WHV is hepatotropic, hence tumors are mas; pgp, p-glycoprotein; HBV, hepatitis B virus; WHV, woodchuck hepatitis liver specific, and (3) HBV and WHV viral DNA sevirus; Mab, monoclonal antibodies; PBS, phosphate-buffered saline; RT-PCR, quences are 70% homologous. 19 In this study, we have reverse-transcribed polymerase chain reaction; cDNA, complementary DNA; PCR, polymerase chain reaction; mRNA, messenger RNA.