Human hepatoma cells secrete low molecular weight, acid-stable protease inhibitors which have stimulatory effects on endothelial cell growth and may inhibit the immune response to tumors. Recombinant cDNA clones for human pancreatic secretory trypsin inhibitor (HPTI) and urinary glycoprotein inhibitor (HI-30) will be isolated and characterized from a human hepatoma cDNA library. The complexity and differences between mRNA species coding for HPTI and HI-30 in normal hepatocytes and hepatoma cells will be determined. HI-30-related antigens in the medium of liver cells are complex as determined by immunochemical analysis. If HI-30 antigens arise by post-translational modification of a single gene product, the complete amino acid sequence of the product will be deduced from cDNA sequence. If HI-30 antigens are separate gene products, unique cDNA probes will be constructed for unique products. cDNA probes will be used to quantitate expression of mRNAs for HPTI and HI-30 antigens in normal hepatocytes and hepatoma cells. The effect of heparin-binding growth factors (HBGF) on expression of HPTI and HI-30 antigens and mRNA will be compared to other hormonal effectors of hepatocyte secretory proteins.
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