BioProject

Aim of study was to determine what was causing the liver tumors in the SART1+/- mice HAF (SART1) is an oxygen-independent ubiquitin ligase for HIF-1α whose physiological role is unknown. More...

Aim of study was to determine what was causing the liver tumors in the SART1+/- mice HAF (SART1) is an oxygen-independent ubiquitin ligase for HIF-1α whose physiological role is unknown. Here we show that HAF knockout mice are embryonic lethal suggesting an essential developmental role. Additionally, male SART1+/- mice spontaneously developed hepatocellular carcinoma (HCC) preceded by steatosis, enhanced liver-neutrophil infiltration and upregulation of HIF-1α in peripheral and liver-infiltrating immune cells. From a cytokine array, we identified a marked (>100-fold) increase in the HIF-1 dependent chemokine, RANTES from SART1+/- -derived Kupffer cells compared to wild-type. Inhibition of RANTES decreased liver neutrophil infiltration, and HCC tumor initiation and growth in SART1+/- mice. These findings establish new roles for HAF in metabolism and immune cell function, and identify RANTES as a novel target for the treatment of HCC. Overall design: RNA isolated (using RNAEasy kit) from 3 pieces of a SART+/- liver tumor (histologically verified as hepatocellular carcinoma), 3 pieces from an uninvolved adjacent liver from the same SART+/- mouse, and 3 pieces from a liver from a wild-type mouse. The 3' IVT PLUS Reagent Kit (Affymetrix, P/N 902416) was used to prepare RNA samples for gene expression profiling analysis: Less...