Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4
and Pten
in mice
J. Clin. Invest. Xiaoling Xu, et al. 116:1843 doi:10.1172/JCI27282 [
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Figure 2
CC formation in Smad4
Co/Co
Pten
Co/Co
Alb-Cre
mice.
(
A–
D) Histologic analysis of livers isolated from 2-month-old
Smad4Co/CoPtenCo/CoAlb-Cre (
A and
B), WT (
C), and
Smad4Co/CoAlb-Cre (
D) mice. Arrows indicate bile ducts. (
E) An H&E-stained liver section showing significantly increased bile duct branching in the liver of a 3-month-old
Smad4Co/CoPtenCo/CoAlb-Cre mouse. The arrow and arrowhead indicate large and small branches, respectively. (
F–
I) Bile duct dysplasia (
F), CC foci with varying histopathology (
G and
H), and well-developed CC (
I) found in
Smad4Co/CoPtenCo/CoAlb-Cre livers. Arrowheads in the insets indicate cells at the mitotic phase. (
J and
K) Bile duct hyperplasia (
J) and CC foci in
PtenCo/CoAlb-Cre (
K) livers. Magnification: ×100 (
A); ×200 (
B–
D and
H); ×400 (
E–
G and
I–
K).