Unsaturated fatty acids are required for continuous proliferation of transformed androgen-dependent cells by fibroblast growth factor family proteins.
Increase in dietary fat intake has been reported to be associated with progression of hormone-dependent cancers. To explore its mechanism, we examined the effects of fatty acids on the growth of androgen-dependent SC-3 cells cloned from mouse mammary cancer (Shionogi carcinoma 115). Their androgen-dependent growth was potentiated by linoleic acid in the defined medium. The effect of linoleic acid on fibroblast growth factor (FGF)-dependent growth was also addressed because androgen had been demonstrated to exert its mitogenic activity on SC-3 cells through an induction of the unique FGF family protein termed as androgen-induced growth factor. Exposure of SC-3 cells to basic FGF or androgen-induced growth factor exhibited only transient growth response. However, simultaneous addition of linoleic acid to the medium sustained the proliferation of FGF-stimulated, but not FGF-unstimulated, cells, although linoleic acid did not exert the significant effect on the process of S-phase entry of basic FGF-stimulated cells. Palmitoleic acid and oleic acid appeared to exert the actions similar to linoleic acid, while stearic acid was without any effect. Neither cyclooxygenase inhibitor nor 5-lipoxygenase inhibitor could block the growth-promoting ability of linoleic acid. Linoleic acid also enhanced their anchorage-independent growth in the presence of basic FGF. These results indicate that these unsaturated fatty acids play a role in sustaining the proliferation of FGF-stimulated SC-3 cells.
Kasayama
S
S
Department of Medicine III, Osaka University Medical School, Japan.
Koga
M
M
Kouhara
H
H
Sumitani
S
S
Wada
K
K
Kishimoto
T
T
Sato
B
B
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D002448:Cell Adhesion; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free; D005227:Fatty Acids / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D016227:Benzoquinones; D016895:Culture Media, Serum-Free; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D008041:Linoleic Acids; D009829:Oleic Acids; D016222:Fibroblast Growth Factor 2; C008757:palmitoleic acid; D019301:Oleic Acid; D013739:Testosterone; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D019787:Linoleic Acid; D007213:Indomethacin