H. Zimmermann et al., THE OVEREXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN IN BILIARY-CIRRHOSIS IN THE RAT AND ITS RELATIONSHIP WITH EPIDERMAL GROWTH-FACTOR RECEPTOR, Journal of hepatology, 23(4), 1995, pp. 459-464
Chronic bile duct obstruction in the rat leads to biliary cirrhosis bu
t maintained hepatocellular mass. We have previously demonstrated tran
slocation of epidermal growth factor receptor to nuclei. It remained u
nclear, however, whether this was due to hepatocyte proliferation and/
or altered handling of epidermal growth factor receptor. Therefore, in
the present investigation we stereologically estimated expression of
proliferating cell nuclear antigen, a marker of the S phase of the cel
l cycle at 1, 2, 3, 7, 14, 21 and 28 days after bile duct ligation. Pr
oliferating cell nuclear antigen positive hepatocytes averaged 2.1+/-3
.6% in sham-operated control animals. This increased to 20.7+/-6.4, 26
.8+/-18.7, 31.3+/-23.9, 42.3+/-16.6 and 24.7+/-28.0% 3, 7, 14, 21 and
28 days after bile duct ligation, respectively (p<0.005 by ANOVA). Thi
s was correlated with the number of epidermal growth factor receptor p
ositive nuclei (r(s)=0.737) and inversely with the maximal binding cap
acity of epidermal growth factor to a crude plasma membrane fraction (
r(s)=0.697) reported previously. We conclude that bile duct ligation i
n the rat induces a significant hepatocellular proliferation as assess
ed by proliferating cell nuclear antigen expression and that this proc
ess could, at least in part, be related to increased nuclear expressio
n of the epidermal growth factor receptor.