Activation of the TGF-beta/Smad signaling pathway in oncogenic transformation by v-Rel

作者：Tiwari Richa; Bargmann William; Bose Henry R Jr^*

来源：Virology, 2011, 413(1): 60-71.

DOI：10.1016/j.virol.2011.02.002

• TGF-beta
• Smad3
• v-Rel
• Rel/NF-kappa B
• Oncogenesis
• Transformation

v-re!, encoded by the avian reticuloendotheliosis virus, is an acutely transforming member of the Rel/NF-kappa B family of transcription factors. Transformation by v-Rel is mediated by the aberrant expression of genes that are normally regulated by Rel/NF-kappa B. Here, we demonstrate activation of the TGF-beta/Smad signaling pathway in Rel transformation. RNA and protein levels of key TGF-beta and Smad family members (TGF-beta 2, TGF-beta 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-beta receptor dramatically reduces soft agar colony formation whereas addition of TGF-beta 2 further promotes transformation. Moreover, Smad3 but not Smad2, is selectively activated as the downstream mediator of TGF-beta signaling. Blocking Smad3 expression or activity inhibits the oncogenic potential of v-Rel. Overall, TGF-beta/Smad signaling is activated at multiple levels and is required for the transforming ability of v-Rd.

• 出版日期2011-4-25