Modulation of MCF-7 breast cancer cell signal transduction by linoleic acid and conjugated linoleic acid in culture

The effects of modifying membrane fatty acid composition on cell growth, ph ospholipase C (PLC) and protein kinase C (PKC) activities, and prostaglandi n E-2 (PGE(2)) secretion were investigated Hormone responsive MCF-7 human b reast cancel cells were incubated in a serum-free medium containing epiderm al growth factor and supplemented with physiologic concentrations (0.18-1.7 8 x 10(-5) M) of linoleic acid (LA) or conjugated linoleic acid (CLA). Lino leic acid stimulated cancer cell growth, while CLA was inhibitory. Suppleme ntation with LA or CLA altered cell membrane composition. Linoleic acid sti mulated PLC activity with or without GTP gamma(S), and tended to increase m embrane PKC activity. However, CLA supplementation did not modify membrane PLC or PKC activity. Prostaglandin E-2 secretion was not influenced by LA o r CLA. These data show that growth inhibition by CLA was not mediated throu gh PLC-, PKC- PGE(2)-dependent signal transduction pathways, suggesting tha t another inhibitory mechanism may be involved. Although biological differe nces appeared to be modest (5-20% of control), the fact that LA and CLA tre atment resulted in significant biological effects at physiologic concentrat ions is relevant, since most human cancers require years to develop.