IFN-gamma-induced change in microtubule organization and alpha-tubulin expression during growth inhibition of lung squamous carcinoma cells

In cultures of KNS-62 cells derived from a human lung squamous cell carcino ma, the initial growth arrest in the continuous presence of interferon-gamm a (IFN-gamma) turned to cytopathic effects after 2 days of treatment. The r emaining viable cells showed grossly distorted morphology, with enlargement and extensions up to 5 cell diameters. The presence of apoptotic cells was shown 3 days after treatment with IFN-gamma. Immunocytochemically, the mic rotubular structures appeared augmented and highly aggregated. The level of alpha -tubulin-specific mRNA was distinctly increased after administration of IFN-gamma, and the amount of extractable alpha -tubulin protein was red uced. In parallel kinetics experiments, growth arrest by serum depletion or by contact inhibition during confluence resulted in reduced levels of alph a -tubulin-specific mRNA and in slightly elevated alpha -tubulin protein. T he IFN-gamma -induced effects suggest interference with assembly or mainten ance of the tubulin cable network, presumably associated with cell deformat ion and cytotoxicity.