Oleic acid blocks epidermal growth factor-activated early intracellular signals without altering the ensuing mitogenic response.
In EGFR-T17 cells, which express high levels of the epidermal growth factor (EGF) receptor, addition of a saturating dose of EGF (10 nM) leads to an increase in Ins(1,4,5)P3/diacylglycerol and also to cytosolic calcium [Ca2+]i due to both intracellular redistribution and influx from extracellular medium. Pretreatment of cells with cis-unsaturated nonesterified fatty acids such as oleic acid (1 to 100 microM) inhibited EGF-stimulated Ins(1,4,5)P3 generation and Ca2+ release from intracellular stores. Furthermore, such a treatment completely suppress Ca2+ influx in a dose-dependent manner. At doses capable of suppressing such early signals, oleic acid did not alter the process of EGF-mediated internalization of the EGF/EGF-receptor complex, suggesting that [Ca2+]i rise did not mediate receptor internalization. EGF-induced cell proliferation assessed by either thymidine incorporation into DNA, direct cell counting, and microscopic observation was not altered by oleic acid, at doses able to block EGF-mediated early signals. In conclusion, suppression of Ins(1,4,5)P3 generation and [Ca2+]i rises by oleic acid did not alter EGF-receptor internalization nor EGF-induced cell mitosis. Such results suggest that [Ca2+]i rise is not instrumental for EGF-stimulated cell proliferation.
Casabiell
X
X
Department of Medicine, Faculty of Medicine, Santiago de Compostela University, Spain.
Zugaza
J L
JL
Pombo
C M
CM
Pandiella
A
A
Casanueva
F F
FF
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004075:Diglycerides / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000502:physiology
D004075:Diglycerides; D008934:Mitogens; D009829:Oleic Acids; D019301:Oleic Acid; D004533:Egtazic Acid; D004815:Epidermal Growth Factor; D015544:Inositol 1,4,5-Trisphosphate; D004247:DNA; D066246:ErbB Receptors; D010738:Type C Phospholipases; D002118:Calcium