ABERRANT METABOLISM OF RETINOID-X RECEPTOR PROTEINS IN HUMAN HEPATOCELLULAR-CARCINOMA

A polyclonal antibody was raised against a recombinant ligand binding domain construct of the human retinoid X receptor (RXR)alpha. This ant ibody reacted with an endogenous 54 kDa nuclear protein from human hep atoma-derived HuH7 cells in immunoblot analyses. Immunoblotting of nuc lear proteins from human hepatocellular carcinomas (HCCs) and their su rrounding tissues revealed the presence of a 44 kDa RXR distinct from the 54 kDa RXR and a dramatic decrease in the relative amounts of 44 k Da RXR to 54 kDa RXR in all HCCs compared with normal tissue. In vitro shift and intracellular conversion from 54 kDa RXR to 44 kDa species were observed with the nuclear extracts of HuH7 cells. Furthermore, tr ansfection of hRXR alpha cDNA into HuH7 cells resulted in the increase of 54 kDa RXR, whereas transfected mouse hepatocytes accumulated 44 k Da RXR. These results strongly indicated that 44 kDa RXR was a physiol ogical proteolytic fragment of 54 kDa RXR and that post-translational metabolism of RXR was impaired in HCC and the HuH7 hepatoma-derived ce ll line.