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Am J Physiol Gastrointest Liver Physiol 269: G335-G345, 1995;
0193-1857/95 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 269, Issue 3 335-G345, Copyright © 1995 by American Physiological Society

ARTICLES

Continuous epithelial cell lines from ADPKD liver cysts exhibit characteristics of intrahepatic biliary epithelium

R. D. Perrone, S. A. Grubman, L. C. Rogers, D. W. Lee, E. Moy, S. L. Murray, V. E. Torres and D. M. Jefferson
Department of Medicine, New England Medical Center, Boston, Massachusetts, USA.

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 medium 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 mo 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.


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