α-Interferon Induces Depletion of Intracellular Iron Content and Up Regulation of Functional Transferrin Receptors on Human Epidermoid Cancer kb Cells

Abstract

We have demonstrated that interferon-α (IFNα) upregulated the epidermal growth factor receptor (EGF-R) on human epidermoid carcinoma cells. Here we report that IFNα induces growth inhibition and upregulation of transferrin receptor (TRF-R) on epidermoid cancer KB cells. IFNα does not alter TRF-R affinity for its ligand and induces a two-fold increase of TRF binding sites. IFNα does not modify receptor internalization and cycling. Intracellular iron levels are known to regulate TRF-R expression: we have, therefore, evaluated whether changes in the iron content could be determined by IFNα. Iron levels are transiently increased after addition of fresh growth medium in untreated controls but not in KB cells exposed for 48 h to IFNα. Iron depletion is however completely reversed 24 h later when maximal TRF-R upregulation occurs in IFN α-treated cells. We suggest that IFNα-induced iron depletion elicits a homeostatic cellular response through upregulation of TRF-R.