Aberrant AFP expression profiles in the absence of Notch. A–D) Immunohistochemical analysis of AFP expression at days 11 and 22 post-PH during 2AAF-PH alone (A and B) as well as in combination with GSI XX treatment (C and D). As seen with the OV-6 staining in the 2AAF-PH group, there is a dramatic increase in AFP expression at day 11 post-PH (A) which drops back down by day 22 post-PH (B). However, in the GSI XX-treated group, although there is a rise in AFP expression at day 11 (C), there is no apparent AFP staining in the oval cells present at day 22 post-PH (D). E) Quantitative real-time polymerase chain reaction analysis for AFP mRNA expression at days 11 and 22 in livers from animals treated with 2AAF-PH alone or 2AAF-PH combined with GSI XX. mRNA expression follows a similar pattern to the protein expression shown via immunohistochemistry above, where AFP increases at day 11 and is virtually nonexistent at day 22 in both treatment groups. A–D 200×.
Abbreviations: GSI XX, γ-secretase inhibitor; PH, partial hepatectomy; 2AAF-PH, 2-acetylaminofluorine implantation followed by 70% surgical resection of the liver; AFP, alpha-fetoprotein.