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Gene expression profiling of 12 month old male C57Bl6 SART+/- liver tumor versus wild-type liver

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE71057 | GEO | 2017/07/14

SECONDARY ACCESSION(S): PRJNA290199

REPOSITORIES: GEO

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