Adaptive mechanisms in the Mdr2-knockout mouse HCC model

We studied the molecular mechanisms of hepatocellular carcinoma (HCC) initiation and promotion using the Mdr2-knockout (Mdr2-KO) mice at pre-cancerous stages of liver disease. These mice lack the liver-specific P-glycoprotein responsible for phosphatidylcholine transport across the canalicular membrane. Portal inflammation ensues at an early age followed by the development of HCC between the ages of 12 and 15 months. Liver tissue samples of Mdr2-KO and control Mdr2-heterozygotes mice aged 3 and 12 months, were subjected to histological, biochemical and gene expression profiling analysis using Affymetrix Mouse Genome Array.

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Katzenellenbogen M, Pappo O, Barash H, Klopstock N, Mizrahi L, Olam D, Jacob-Hirsch J, Amariglio N, Rechavi G, Mitchell LA, Kohen R, Domany E, Galun E, Goldenberg D