COMPARATIVE PHENOTYPIC STUDIES OF DUCT EPITHELIAL-CELL LINES DERIVED FROM NORMAL HUMAN PANCREAS AND PANCREATIC-CARCINOMA

We have investigated the mRNA/protein expression of several tyrosine k inase receptors, growth factors, and p16(INK4A) cyclin inhibitor in ce ll lines derived from normal human pancreatic duct epithelium (HPDE) a nd compared them with those of five pancreatic ductal carcinoma cell l ines, Cultured HPDE cells express low levels of epidermal growth facto r receptor (EGFR), erbB2, transforming growth factor (TGF)-alpha, Met/ hepatocyte growth factor receptor (HGFR), vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF), They also express ed high levels of amphiregulin but did not express EGF and cripto. The expression levels were similar in primary normal HPDE cells and those expressing transfected EbE7 genes of human papilloma virus-16, but th eir immortalization appeared to enhance the expression of EGFR and Met /HGFR, In comparison, pancreatic carcinoma cell Lines commonly demonst rated overexpression of EGFR, erbB2, TGF-alpha, Met/HGFR, VEGF, and KG F, but they consistently showed marked down-regulation of amphiregulin mRNA expression, In contrast to all carcinoma cell lines that showed deletions of the p16 gene, HPDE cells consistently demonstrated normal p16 genotype and its mRNA expression, This is the first report that c ompares the phenotypic expression of cultured pancreatic ductal carcin oma cells with epithelial cell lines derived from normal human pancrea tic ducts, The findings confirm that malignant transformation of human pancreatic duct cells commonly results in a deregulation of expressio n of various growth factors and receptors.