title: Activation of the TGF-β/Smad signaling pathway in oncogenic transformation by v-Rel.
abstract: v-rel, encoded by the avian reticuloendotheliosis virus, is an acutely transforming member of the Rel/NF-κB family of transcription factors. Transformation by v-Rel is mediated by the aberrant expression of genes that are normally regulated by Rel/NF-κB. Here, we demonstrate activation of the TGF-β/Smad signaling pathway in Rel transformation. RNA and protein levels of key TGF-β and Smad family members (TGF-β2, -β3, TGF-β type II receptor, and Smad3) are upregulated in v-Rel transformed cells with little to no change in c-Rel-expressing cells. Treatment of v-Rel transformed lymphoid cells with kinase inhibitors of the TGF-β receptor dramatically reduces soft agar colony formation whereas addition of TGF-β2 further promotes transformation. Moreover, Smad3 but not Smad2, is selectively activated as the downstream mediator of TGF-β signaling. Blocking Smad3 expression or activity inhibits the oncogenic potential of v-Rel. Overall, TGF-β/Smad signaling is activated at multiple levels and is required for the transforming ability of v-Rel.
authors.affiliation: Section of Molecular Genetics and Microbiology and the Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712-1095, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Tiwari
authors.forename: William
authors.initials: W
authors.lastname: Bargmann
authors.forename: Henry R
authors.initials: HR
authors.lastname: Bose
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002645:Chickens; D005786:Gene Expression Regulation; D020572:Oncogene Proteins v-rel / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D017986:Reticuloendotheliosis Viruses, Avian; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D020572:Oncogene Proteins v-rel; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta