In preliminary studies we have observed the overexpression and overproduction of P-glycoprotein in precancerous liver and hepatocellular carcinoma (HCC) tissue from woodchuck hepatitis virus (WHV) carrier woodchucks and its absence or low level in uninfected liver. Immunocytochemical studies have localized the protein to the canalicular face of hepatocytes. Northern blot analysis of total cellular RNA using cDNA probes specific for P-glycoprotein has identified a high level of transcription in tumor tissue. These studies provide the foundation for a pilot project to study the expression of P-glycoprotein in different pathophysiological states in the liver and the possible role of WHV in P- glycoprotein expression. The tools are available to study both the cellular localization and the molecular mechanism of transcription and translation of the protein. These studies may enable us to understand the selective mechanisms which result in the development of clonal tumors which express multidrug resistance.
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