By combining genomics and metabolomics, we found that the transition from inflammation to cancer in Mdr2-/- mice was linked to the sustained transcriptional activation of metabolic detoxification systems and transporters by the Constitutive Androstane Receptor (CAR), a hepatocyte-specific nuclear receptor.
Non-synonymous SNPs in ABCB4 have now been described in patients with liver cancer or with inflammatory liver diseases that are known to predispose to cancer, but data showing that the SNPs are sufficiently deleterious to be an etiological factor are lacking.
Our results suggest that PSK may augment anti-tumour action via genes including multidrug resistance protein 3 (MRP3), lymphotactin (Lptn), transgelin (TAGLN), and Pirin, without disturbing cell-cycle progression, and may deserve a large clinical trial in cancer therapy.
Antibody 6/1G may be useful in defining a role for MDR-3 in malignancy and drug resistance, as well as in certain liver diseases such as progressive familial intracholeostasis.