Parathyroid hormone-related peptide is expressed and rapidly inducible in human liver cell cultures that have a bile duct phenotype

Parathyroid hormone-related peptide is the major factor responsible for hypercalcemia of malignancy. There is increasing evidence that parathyroid hormone-related peptide also plays an important role in the growth and differentiation of both neoplastic and non-neoplastic cells. Recently we found that reactive human bile ductules and cholangiocarcinomas, but not normal bile ducts, human hepatocytes nor hepatocellular carcinomas, express parathyroid hormone-related peptide and we speculated that parathyroid hormone-related peptide may function as a growth and differentiation factor for bile ductular epithelial cells. Using a specific polyclonal antibody for immunostaining and a digoxigenin-random prime-labeled probe for in situ hybridization assay, we found that only cell lines with a bile duct phenotype expressed parathyroid hormone-related peptide and its mRNA. HepG2 cells with hepatocellular phenotype (CK19-, CK7-, CK8+, CK18+, albumin+) do not express parathyroid hormone-related peptide. However, A16 (HepG2 derived cell line) expressing bile duct marker CK19, also expressed parathyroid hormone-related peptide, while hepatocyte markers CK8, CK18, CALLA and albumin were negative. In addition, the H1 cell line (adult human hepatocytes immortalized in our laboratory by SV40 DNA transfection, passaged at least 40 times and cultured for 13 months) expressed bile duct marker CK7 and parathyroid hormone-related peptide, while hepatocyte markers CK8, CK18, CALLA and albumin were negative. Previous studies demonstrated that parathyroid hormone-related peptide gene expression in keratinocytes can be modulated by serum, growth factors and cycloheximide although there is a species and cellular specificity.(ABSTRACT TRUNCATED AT 250 WORDS)