IFN-γ-Induced Change in Microtubule Organization and α-Tubulin Expression During Growth Inhibition of Lung Squamous Carcinoma Cells

Abstract

In cultures of KNS-62 cells derived from a human lung squamous cell carcinoma, the initial growth arrest in the continuous presence of interferon-γ (IFN-γ) turned to cytopathic effects after 2 days of treatment. The remaining 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-γ. Immunocytochemically, the microtubular structures appeared augmented and highly aggregated. The level of α-tubulin-specific mRNA was distinctly increased after administration of IFN-γ, and the amount of extractable α-tubulin protein was reduced. In parallel kinetics experiments, growth arrest by serum depletion or by contact inhibition during confluence resulted in reduced levels of α-tubulin-specific mRNA and in slightly elevated α-tubulin protein. The IFN-γ-induced effects suggest interference with assembly or maintenance of the tubulin cable network, presumably associated with cell deformation and cytotoxicity.