Interactions between epidermal growth factor-mediated autocrine regulation and linoleic acid-stimulated growth of a human prostate cancer cell line.
Human prostate cancer (PC) cell lines possess epidermal growth factor (EGF) receptors and secrete EGF-related polypeptides. We used an EGF receptor-blocking antibody (anti-EGF.R) to demonstrate a functional autocrine loop, as well as the interaction between this and the effects of linoleic acid (LA), an omega-6 fatty acid, on PC cell growth. The anti-EGF.R competed effectively with [125I]EGF for receptors on DU145 PC cells, and on a high-passage DU145 variant (DU145M); when added to the culture medium, it suppressed both DU145 and DU145M cell growth in a dose-dependent manner. LA, a precursor for eicosanoid synthesis, had little effect on DU145 cell growth rate but stimulated DU145M growth in a concentration-related manner over a range of 0.25-2.0 micrograms/ml. anti-EGF.R (10(-9) M) caused suppression of LA-stimulated growth of DU145M cells in serum-free medium, which was prevented by the addition of 2 nM EGF. We conclude that an EGF.R-mediated autocrine loop is involved in PC cell growth regulation and that at least one site of action may be the synthesis of eicosanoids from their LA precursor.
Connolly
J M
JM
Division of Nutrition and Endocrinology, Naylor Dana Institute for Disease Prevention, Valhalla, NY 10595.
Rose
D P
DP
D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D008041:Linoleic Acids; D004815:Epidermal Growth Factor; D019787:Linoleic Acid; D066246:ErbB Receptors