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Key among the pathways' mediating growth factor action is the MAP kinase signaling cascade and the PI\u20103 kinase pathway with its downstream effector mTOR. We postulated that farnesylthiosalicylic acid (FTS), a novel anti\u2010Ras drug, could effectively inhibit hormone\u2010dependent breast cancer because Ras activates both the MAP kinase and the PI3 kinase pathways. Wild\u2010type MCF\u20107 cells and a long\u2010term estrogen\u2010deprived subline (LTED) were used to examine the effect of FTS on cell growth and on several biochemical parameters. FTS inhibited growth of both cell lines by reducing proliferation and inducing apoptosis. These effects correlated best with blockade of phosphorylation of PHAS\u2010I and p70 S6 kinase, 2 downstream effectors of mTOR. We observed only minimal inhibition of Akt, an effector upstream of mTOR. Taken together, these findings demonstrate a novel effect of FTS to inhibit mTOR signaling and also suggest that mTOR has a key role in breast cancer cell proliferation. Unexpectedly, only minimal inhibition of MAP kinase occurred in response to FTS at concentrations that markedly reduced cell growth. These later data provide support for the concept that FTS exerts its effects predominantly by blocking mTOR and to a lesser effect by inhibition of MAP kinase in breast cancer cells. Supplementary material for this article can be found on the <jats:italic>International Journal of Cancer<\/jats:italic> website at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.interscience.wiley.com\/jpages\/0020-7136\/suppmat\/index.html\">http:\/\/www.interscience.wiley.com\/jpages\/0020\u20107136\/suppmat\/index.html<\/jats:ext-link>. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.21222","type":"journal-article","created":{"date-parts":[[2005,6,14]],"date-time":"2005-06-14T19:48:59Z","timestamp":1118778539000},"page":"746-754","source":"Crossref","is-referenced-by-count":27,"title":["Farnesylthiosalicylic acid blocks mammalian target of rapamycin signaling in breast cancer 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