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In\n                    <jats:sup>V600E<\/jats:sup>\n                    BRAF cells, this output is comprised of 52 genes, including transcription factors that regulate transformation and members of the dual specificity phosphatase and Sprouty gene families, feedback inhibitors of ERK signaling. No such genes were identified in RTK tumor cells, suggesting that ERK pathway signaling output is selectively activated in BRAF mutant tumors. We find that RAF signaling is feedback down-regulated in RTK cells, but is insensitive to this feedback in BRAF mutant tumors. Physiologic feedback inhibition of RAF\/MEK signaling down-regulates ERK output in RTK cells; evasion of this feedback in mutant BRAF cells is associated with increased transcriptional output and MEK\/ERK-dependent transformation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0900780106","type":"journal-article","created":{"date-parts":[[2009,2,27]],"date-time":"2009-02-27T21:11:49Z","timestamp":1235769109000},"page":"4519-4524","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":565,"title":["<sup>V600E<\/sup>\n                    BRAF is associated with disabled feedback inhibition of RAF\u2013MEK signaling and elevated transcriptional output of the pathway"],"prefix":"10.1073","volume":"106","author":[{"given":"Christine A.","family":"Pratilas","sequence":"first","affiliation":[{"name":"Departments of aPediatrics,"},{"name":"Molecular Pharmacology and Chemistry,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry S.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Computational Biology, and"},{"name":"Department of Physiology and Biophysics, Weill Cornell Graduate School of Medical Science, New York, NY 10065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Ye","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology and Chemistry,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes","family":"Viale","sequence":"additional","affiliation":[{"name":"Molecular Biology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Sander","sequence":"additional","affiliation":[{"name":"Computational Biology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Solit","sequence":"additional","affiliation":[{"name":"Medicine,"},{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal","family":"Rosen","sequence":"additional","affiliation":[{"name":"Medicine,"},{"name":"Molecular Pharmacology and Chemistry,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2009,3,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(97)80061-0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202367"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00766"},{"key":"e_1_3_3_4_2","first-page":"6997","article-title":"BRAF and RAS mutations in human lung cancer and melanoma","volume":"62","author":"Brose MS","year":"2002","unstructured":"MS Brose, et al., BRAF and RAS mutations in human lung cancer and melanoma. 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