Continuous epithelial cell lines from adpkd liver cysts exhibit
characteristics of intrahepatic biliary epithelium.
Perrone, Ronald D., Shelley A. Grubman, Linda C. Rogers, Des W. Lee,
E. Moy, Sandra L. Murray, Vicente E. Torres, and Douglas M.
Jefferson.
Departments of Medicine and Pediatrics, New England Medical Center,
Boston Massachusetts 02111, Department of Medicine, Mayo Foundation,
Rochester Minnesota 55905 and Department of Physiology, Tufts
University School of Medicine, Boston Massachusetts 02111
APStracts 2:0105G, 1995.
We have produced continuous cell lines using retroviral transduction
of SV40 large T antigen into epithelial cells removed from the lumen
of liver cysts from four female patients with autosomal dominant
polycystic kidney disease (ADPKD). Liver cyst-derived epithelial
(LCDE) cell lines are grown in a hormonally-supplemented media in the
presence of lethally-irradiated NIH-3T3 fibroblast coculture. LCDE
cells maintain their epithelial appearance and are positive for the
biliary-specific markers cytokeratin 7 and 19 and [gamma]-glutamyl
transpeptidase while being negative for hepatocyte markers. SV40
large T antigen is localized to the cell nucleus. LCDE cells have
been grown continuously for periods exceeding 12 months and 25
passages (170 population doublings). LCDE cells exhibit intracellular
pH regulatory pathways that, with one exception, are similar to those
found in normal intrahepatic biliary epithelium. These LCDE cell
lines exhibit impaired alkalinization in response to Cl-
-substitution. This finding is suggestive of decreased function or
abundance of a Cl--HCO3- anion exchanger and could account for the
failure of ADPKD hepatic cysts to secrete HCO3- in response to
secretin.
Received 4 November 1994; accepted in final form 10 April 1995.
APS Manuscript Number G442-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.