alpha-Interferon potentiates epidermal growth factor receptor-mediated effects on human epidermoid carcinoma KB cells.
The molecular mechanisms underlying the growth inhibition of human tumor cells induced by recombinant interferon-alpha (IFN alpha) are mostly unknown. It has been proposed that this effect could be related to down-regulation and/or impaired function of peptide growth factor receptors (PGF-Rs) in tumor cells exposed to IFN alpha. However, we have previously described that IFN alpha-induced growth inhibition of human epidermoid carcinoma cells is paralleled by up-regulation of epidermal growth factor receptor (EGF-R). Here we report that an increase in EGF-R synthesis is detectable after 3 hr of exposure to cytostatic concentration of IFN alpha in epidermoid KB tumor cells. In these experimental conditions IFN alpha does not depress and even potentiates EGF-R function. IFN alpha-treated KB cells retain sensitivity to the cytotoxic activity of the anti-EGF-R 225 monoclonal antibody (MAb), which acts through receptor blockade, and are sensitized to the growth-promoting effect of EGF. EGF-induced tyrosine (tyr) phosphorylation both of total cellular protein extracts and of the immunoprecipitated EGF-R is increased in IFN alpha-treated cells. We conclude that a cross-talk between IFN alpha and EGF occurs in KB cells since IFN alpha, at cytostatic concentration, potentiates the effects mediated by the EGF-R.
Caraglia
M
M
Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II di Napoli, Italy.
Leardi
A
A
Corradino
S
S
Ciardiello
F
F
Budillon
A
A
Guarrasi
R
R
Bianco
A R
AR
Tagliaferri
P
P
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007624:KB Cells; D007700:Kinetics; D008970:Molecular Weight; D011994:Recombinant Proteins; D013997:Time Factors; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors