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-Interferon Down-Regulates Epidermal Growth Factor Receptors on Renal Carcinoma Cells: Relation to Cellular Responsiveness to the Antiproliferative Action of -Interferon¹

Laboratory of Cell Physiology and Virology, Rockefeller University [B. L. E., L. M. P.], and Laboratory of Mammalian Cell Transformation, Memorial Sloan-Kettering Cancer Center [D. M. N., A. P. A.] New York, New York 10021

The CaKi-I line of renal carcinoma (RC) cells is highly sensitive to the antiproliferative effect of human leukocyte interferon (IFN-). These RC cells express high numbers of cell surface receptors for epidermal growth factor (EGF), and EGF stimulates their proliferation. IFN- 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-, IFN- 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-. While IFN- does not affect the level of total cellular message or total polyadenylated message for the EGFR, IFN- treatment decreases the level of cytoplasmic EGFR message. Analysis of polysome distribution of cellular mRNAs indicates that IFN- treatment results in an accumulation of EGFR mRNA in lighter polysome fractions, consistent with a partial block in translational elongation. Thus, IFN- 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- on RC proliferation.

¹ 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.

² To whom requests for reprints should be addressed. Present address: Department of Pathology, University of Tennessee College of Medicine, Memphis, TN 38163.

Received 3/13/91. Accepted 8/26/91.

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