Upregulation of epidermal growth factor receptor induced by alpha-interferon in human epidermoid cancer cells.
Unregulated or increased expression of epidermal growth factor receptor (EGF-R) is a common event in neoplastic transformation; modulation of such a receptor by physiological agents could be, therefore, of clinical interest. We have studied the binding ability, the availability at cell surface, and the synthesis of EGF-R in the A431 and KB human epidermoid cancer cell lines after treatment with recombinant alpha-interferon (IFN-alpha). After 48 h of treatment, IFN-alpha induces, in both cell lines, growth inhibition and enhances class I major histocompatibility HLA complex expression, which is a common marker of IFN action. [125I]EGF total binding assessed after 48 h of treatment with IFN-alpha shows a dose-dependent upregulation of EGF-R binding capacity. Saturation plots of the binding data show that IFN-alpha treatment does not dramatically alter the affinity of the EGF-R and indicate that IFN-alpha only increases the number of low affinity receptors. We show that this effect is due to a specific increase in the synthesis of the receptor protein, as assessed by immunoprecipitation of [35S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed an increase of EGF-R proteins at cell surface without major changes in the morphology of the cells. Taken together, these results indicate that IFN-alpha consistently induces both the binding capacity and the synthesis of EGF-R in human epidermoid cancer cells and suggest the use of such a mechanism for new anticancer therapies.
Budillon
A
A
Cattedra di Oncologia Medica, II Facoltà di Medicina, Università Napoli, Italy.
Tagliaferri
P
P
Caraglia
M
M
Torrisi
M R
MR
Normanno
N
N
Iacobelli
S
S
Palmieri
G
G
Stoppelli
M P
MP
Frati
L
L
Bianco
A R
AR
D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis / Q000187:drug effects*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I / Q000187:drug effects; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D016253:Microscopy, Immunoelectron; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D006680:HLA Antigens; D007370:Interferon Type I; D004815:Epidermal Growth Factor; D066246:ErbB Receptors