alpha-Interferon down-regulates epidermal growth factor receptors on renal carcinoma cells: relation to cellular responsiveness to the antiproliferative action of alpha-interferon.
The CaKi-I line of renal carcinoma (RC) cells is highly sensitive to the antiproliferative effect of human leukocyte interferon (IFN-alpha). These RC cells express high numbers of cell surface receptors for epidermal growth factor (EGF), and EGF stimulates their proliferation. IFN-alpha 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-alpha, IFN-alpha 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-alpha. While IFN-alpha does not affect the level of total cellular message or total polyadenylated message for the EGFR, IFN-alpha treatment decreases the level of cytoplasmic EGFR message. Analysis of polysome distribution of cellular mRNAs indicates that IFN-alpha treatment results in an accumulation of EGFR mRNA in lighter polysome fractions, consistent with a partial block in translational elongation. Thus, IFN-alpha 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-alpha on RC proliferation.
Eisenkraft
B L
BL
Laboratory of Cell Physiology and Virology, Rockefeller University, New York, New York.
Nanus
D M
DM
Albino
A P
AP
Pfeffer
L M
LM
D002292:Carcinoma, Renal Cell; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007680:Kidney Neoplasms; D007700:Kinetics; D011061:Poly A / Q000235:genetics; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D012313:RNA / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger; D011994:Recombinant Proteins
D007370:Interferon Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011061:Poly A; D004815:Epidermal Growth Factor; D012313:RNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D066246:ErbB Receptors