THE OVEREXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN IN BILIARY-CIRRHOSIS IN THE RAT AND ITS RELATIONSHIP WITH EPIDERMAL GROWTH-FACTOR RECEPTOR

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.