Lack of mda-6/WAF1/CIP1-mediated inhibition of cyclin-dependent kinases in interferon-α resistant murine B16 melanoma cells

Previously we demonstrated that IFN-α augments mda-6/WAF1 and inhibits cyclin-dependent kinases in a p53-independent fashion in B16 murine melanoma cells. On the other hand, IFN-γ activates p53 expression without affecting the mda-6/WAF1 system. Combination of the two IFNs is additive. B16 cells acquire IFN-α resistant but IFN-γ sensitive phenotype after long term IFN-α treatment (B16α cells). Here we demonstrate the absence of mda-6/WAF1-associated repression of cyclindependent kinases, but the existence of p53-dependent c-myc inhibition in IFN-γ-treated B16α cells. Clearly, selective desensitization of IFN-α related growth regulation does not influence the IFN-γ associated pathway. Our results further support the coexistence of distinct growth regulatory mechanisms in B16 cells that can be activated by different IFN-types independently of each other.