DERANGEMENTS IN THE ACTIVIN-FOLLISTATIN SYSTEM IN HEPATOMA-CELLS

Background/Aims: The growth of normal hepatocytes is regulated by the activin-follistatin system. The aim of this study was to investigate t he activin-follistatin system in hepatoma cells. Methods: The producti on and action of activin and follistatin in human hepatoma cell lines were examined. Activin A and follistatin were measured by bioassay and protein-binding assay, respectively. Results: Activin A inhibited cel l growth in HepG2 cells but not in either PLC/PRF/5 or HLE cells. Howe ver, the effect of activin A in HepG2 cells was attenuated at high cel l density. In HepG2 cells, two classes of activin-binding sites were e xpressed, and affinity cross-linking showed that I-125-activin A bound specifically to three proteins with molecular weights of 48, 67, and 94 kilodaltons. In PLC/PRF/5 cells, a single class of binding site was observed, and the binding capacity was approximately 60% of the capac ity in HepG2 cells. Virtually no I-125-activin A binding was detected in HLE cells. Bioactivity and messenger RNA for activin A were undetec table in three cell lines. In contrast, follistatin was released from three cell lines. Conclusions: Multiple alterations in the activin-fol listatin system were found in three hepatoma cell lines. The accelerat ed growth observed in hepatoma cells may be caused, at least partly, b y the attenuation of the action of activin A.