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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#_4 http://www.w3.org/ns/prov#value Although the growth-inhibitory effect of TGF-B is believed to be mediated by the Smad dependent TGF-B signaling pathway, there have been reports of TGF-B mediated inhibition of proliferation in Smad4 null cells.22 Proposed alternative mechanisms for resistance to TGF-B include decreased expression of TBRI,34 TBRII,35 or TBRIII36 on the cell surface; increased expression of the inhibitory Smad, Smad7; repression of TGF-B signaling by a variety of oncoproteins including p53,38 Myc,39 E1A,40 Ras,41 Ski/ SnoN,42,43 and Evi-1 44; reduced expression or inactivation of tumor suppressors that directly regulate the TGF-B signaling pathway including Menin,45 Disabled-2 ,46 and RUNX3; and activation of other signaling pathways includings protein kinase C (PKC). TGF-B is able to increase the production of mitogenic growth factors, including platelet-derived growth factor,51 fibroblast growth factor,52 TGF-B,53 and connective tissue growth factor,54 and to increase expression of the platelet derived growth factor receptor,55 and the epithelial growth factor receptor.56 In addition, TGF-B can activate Smad independent pathways, including the Ras/Raf/MAPK pathway,20-22,57,58 which often mediates the proliferative signal of growth factors. Indeed, it is in conjunction with oncogenic forms of Ras (Ha-Ras or Ki-Ras), that TGF-B drives Smad-independent proliferation of human colon and prostate cancer cells.3,49 http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/15774796 http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/15774796 http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#_4 http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA#pubinfo http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA http://purl.org/dc/terms/created 2014-07-03T14:30:33.478+02:00 http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAUDCYSMPNqxtkZmdZr042ghd-mrQcqU_Fze3u3BnZAmA http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234