We investigated the effects of linoleic acid and eicosanoid synthesis inhibitors on the growth, DNA synthesis, and c-myc oncogene expression of human breast cancer cell lines. The cell growth of all cell lines examined was stimulated by linoleic acid, although the optimal concentration of linoleic acid for the growth stimulation differed among the cell lines. The growth stimulation of MCF7 and MDA-MB-435 cells was not dependent on the amount of released prostaglandin E(2) but their growth-concentration curve showed the same pattern as that of released leukotriene B-4. Moreover, linoleic acid stimulated the expression of c-myc mRNA in MCF7 cells without the presense of estrogen. Indomethacin as a cyclooxygenase inhibitor did not inhibit the c-myc expression in MCF7, but a lipoxygenase inhibitor, esculetin, markedly inhibited the c-myc expression in MCF7 affected by linoleic acid. These results suggest that linoleic acid has a direct mitogenic effect on breast cancer cells, and its mechanism is distinct from hormonal stimulation, Moreover, metabolites of lipoxygenase rather than those of cyclooxygenase may play an important role in the c-myc oncogene expression affected by linoleic acid.

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