Fragments of human oncoprotein MDM2 reveal variable distribution within and on cultivated human hepatoma cells

Human oncoprotein MDM2 reveals a MHC class I binding motif HMDM441 characte rizing MDM2 as a potential tumor antigen. To analyze the distribution of MD M2 proteins containing this motif in liver cancer cells we produced rabbit anti-HMDM441 serum. The novel antibodies bound to an MDM2 fragment of appro ximately 55 kDa which lacked the N-terminal region and was present in lysat e and supernatant of a human hepatoma cell line overexpressing normal 90-kD a MDM2. The 55-kDa fragment was detected in the cytoplasm and nucleoli and at the nuclear envelope of hepatoma cells, whereas normal hepatocytes were negative. Double-fluorescence labeling indicated that the MDM2 fragments an d MHC class I molecules were coexpressed on the surface of the hepatoma cel ls. Further studies must clarify whether MDM2 fragments containing motif HM DM441 are novel targets of immunotherapy and immunochemical tumor diagnosis . (C) 2001 Academic Press.