This finding strongly supports the notion that overexpression of CD151/MMP9/angiogenesis is intimately involved in the metastasis of HCC. On the basis of the available existing data, although we cannot completely exclude a role for other angiogenic factors, such as VEGF and MMP2, in neoangiogenesis of HCC, we hold

that the CD151/MMP9/angiogenesis cascade probably is one of the factors controlling tumor angiogenesis in HCC. This provides a perspective on how tumor cells can induce tumor neoangiogenesis and how they are implicated in metastasis. In conclusion, we have examined the role of CD151-dependent tumor angiogenesis in the progression of HCCs. CD151-dependent Tamoxifen mw tumor angiogenesis may be mediated by MMP9 via the PI3K/Akt/GSK-3β/Snail pathway. More importantly, our findings highlight the possibility of CD151 being used as a high-priority FK506 chemical structure target for antiangiogenesis therapy in HCC. The authors thank Dr. Yong-Xiang Jiang for construction of the mouse cornea micropocket angiogenesis model. They also thank Professor Fei Yuan and Dr. Chen-Li Feng for assaying neoangiogenesis in the cornea and Dr. Yi-Zhou He for drawing

the working model. Additional Supporting Information may be found in the online version of this article. “
“Pregnancy alters bile acid homeostasis and can unmask cholestatic disease in genetically predisposed but otherwise asymptomatic individuals. In this report, we show that normal pregnant mice have raised hepatic bile acid levels in the presence of procholestatic gene expression. The nuclear receptor farnesoid X receptor (FXR) regulates the transcription of the majority of these genes, and we show that both ablation and activation of Fxr prevent the accumulation of hepatic

bile acids during pregnancy. These observations suggest that the function of Fxr may be perturbed during gestation. In subsequent in vitro experiments, serum from pregnant mice and humans was found to repress expression of the Fxr target gene, small heterodimer partner (Shp), in liver-derived Fao cells. Estradiol or estradiol metabolites may contribute to this effect because coincubation with the estrogen receptor (ER) antagonist fulvestrant (ICI medchemexpress 182780) abolished the repressive effects on Shp expression. Finally, we report that ERα interacts with FXR in an estradiol-dependent manner and represses its function in vitro. Conclusion: Ligand-activated ERα may inhibit FXR function during pregnancy and result in procholestatic gene expression and raised hepatic bile acid levels. We propose that this could cause intrahepatic cholestasis of pregnancy in genetically predisposed individuals. HEPATOLOGY 2010 The synthesis, metabolism, and enterohepatic circulation of bile acids is tightly regulated by nuclear hormone receptors.1 Farnesoid X receptor (FXR) is required for the basal maintenance of the enterohepatic circulation and its response to bile acid challenge.