IFNs down-regulate β-catenin activation and signaling activity. Lung cancer cell lines, A549 (A) and Calu-3 (C), were left untreated or treated with IFNα (100 ng/ml), IFNγ (100 ng/ml) or IFNλ1 (100 ng/ml) for 24 hrs before transfection with TOPflash luciferase and Renilla luciferase constructs. After 4 hrs, the cells were cultured with or without initial treatment of different IFNs. Dual luciferase activity was measured 24 hrs later. Data shown is normalized to Renilla activity. A549 (B) and Calu-3 (D) were treated with or without IFNα (100 ng/ml), IFNγ (100 ng/ml) or IFNλ1 (100 ng/ml) for 48 hrs and expression of hypophosphorylated/active β-catenin level was measured by flow cytometry. Data represent a minimum of three experiments and asterisks denote P<0.05 in comparison to untreated samples.