The CaKi-I line of renal carcinoma (RC) cells is highly sensitive to the antiproliferative effect of human leukocyte interferon (IFN-α). These RC cells express high numbers of cell surface receptors for epidermal growth factor (EGF), and EGF stimulates their proliferation. IFN-α blocks EGF-stimulated proliferation of these cells and down-regulates EGF receptors (EGFR) by inhibiting EGFR synthesis. Although EGF stimulates the proliferation of RC cells resistant to the antiproliferative action of IFN-α, IFN-α treatment does not block the EGF-stimulated proliferation of these cells and has no effect on EGFR expression. Thus, the down-regulation of EGFR is specific for RC cells sensitive to IFN-α. While IFN-α does not affect the level of total cellular message or total polyadenylated message for the EGFR, IFN-α treatment decreases the level of cytoplasmic EGFR message. Analysis of polysome distribution of cellular mRNAs indicates that IFN-α treatment results in an accumulation of EGFR mRNA in lighter polysome fractions, consistent with a partial block in translational elongation. Thus, IFN-α regulates the expression of EGFR and possibly other growth-related proteins by post-transcriptional mechanisms, which may play an important part in the complex inhibitory action of IFN-α on RC proliferation.
This work was supported by NIH Grant GM36716 (L. M. P.), the Society for Memorial Sloan Kettering Cancer Center, and a National Kidney Foundation Young Investigator Award (DMN). L. M. P. is a Scholar of the Leukemia Society of America.