Interferon-Beta Signaling Contributes To Ras Transformation

Increasing evidence has pointed to activated type I interferon signaling in tumors. However, the molecular basis for such activation and its role in tumorigenesis remain unclear. In the current studies, we report that activation of type I interferon (IFN) signaling in tumor cells is primarily due to elevated secretion of the type I interferon, IFN-beta. Studies in oncogene-transformed cells suggest that oncogenes such as Ras and Src can activate IFN-beta signaling. Significantly, elevated IFN-beta signaling in Ras-transformed mammary epithelial MCF-10A cells was shown to contribute to Ras transformation as evidenced by morphological changes, anchorage-independent growth, and migratory properties. Our results demonstrate for the first time that the type I IFN, IFN-beta, contributes to Ras transformation and support the notion that oncogene-induced cytokines play important roles in oncogene transformation.