Interferons inhibit EGF-stimulated cell growth and reduce EGF binding in human breast cancer cells.
CG-5 estrogen-sensitive human breast cancer cells contain specific Epidermal Growth Factor receptors (EGF-R, Kd = 0.09-0.17 nM) and respond to the mitogenic effect of EGF. The increase in cell proliferation has been observed starting with very low concentrations of EGF (10-12M) and was statistically significant at all doses. Nevertheless, cell growth stimulation was emphasized when cells were grown under stringent culture conditions. When cells were exposed to 100 IU/ml of natural beta-interferon (n beta-IFN) the binding of EGF to the cell membrane was reduced after 72 hours of treatment, while the exposure of CG-5 cells to 1000 IU/ml of n beta-IFN resulted in an EGF-R reduction which started after 48 hours and became statistically significant after 72-120 hours. If CG-5 cells were treated with 1000 IU/ml of recombinant alpha 2b-interferon (ra2b-IFN) this reduction was observed after 168 hours of exposure to the drug. Both the IFNs abolished EGF-stimulated cell growth. Our results indicate that IFN treatment down-regulates EGF-R in estrogen-sensitive breast cancer cells and suggests that this down-regulation may be involved in the inhibitory action of IFN on cell growth.
Iacopino
F
F
Institute of Histology and Embryology, Catholic University of the Sacred Heart, Faculty of Medicine, Rome, Italy.
Ferrandina
G
G
Scambia
G
G
Benedetti-Panici
P
P
Mancuso
S
S
Sica
G
G
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007700:Kinetics; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D016899:Interferon-beta; D066246:ErbB Receptors