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Farnesyl thiosalicylic acid also inhibited the growth of U87 cells. The way in which Ras inhibition affects U87 cell proliferation was not clear. Here we applied a computational method in which gene expression profile clustering is combined with promoter sequence analysis to obtain global dissection of the transcriptional response to farnesyl thiosalicylic acid in U87 cells. The analysis revealed a prominent Ras\u2010dependent cell\u2010cycle arrest response, in which a major component is highly enriched for the binding\u2010site signature of the transcription factor E2F1. Electrophoretic mobility shift assays together with E2F\u2010luciferase reporter assays showed that E2F1 was inactivated by the Ras inhibitor. Inhibition of Ras by farnesyl thiosalicylic acid promoted proteasomal degradation of cyclin D1, with a concomitant decrease in phosphorylated retinoblastoma protein accompanied by downregulation of E2F1 and decreased expression of key E2F1\u2010regulated genes critical for cell\u2010cycle progression. U87 cell growth arrest induced by farnesyl thiosalicylic acid was overridden by constitutive expression of E2F1. Thus, downregulation of E2F1 and of hypoxia\u2010inducible factor\u20101\u03b1 represents 2 distinct arms of the antioncogenic effect of Ras inhibitors in glioblastoma. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.21735","type":"journal-article","created":{"date-parts":[[2006,2,22]],"date-time":"2006-02-22T22:47:08Z","timestamp":1140648428000},"page":"527-538","source":"Crossref","is-referenced-by-count":21,"title":["E2F1 identified by promoter and biochemical analysis as a central target of glioblastoma cell\u2010cycle arrest in response to ras 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