title: [RAC3 overexpression is a transforming and proliferative signal that contributes to tumoral development].
abstract: RAC3 has been firstly characterized as a nuclear receptor coactivator that is found in limited amounts in normal cells, but is over-expressed in tumors and is also an NF-kB coactivator. Although the mechanisms involved in its over-expression are not clear, it is well known that it enhances resistance to apoptosis. In this work, we investigated if there are any additional mechanisms by which RAC3 may contribute to tumor development and if TNF-a, an inflammatory cytokine that is found at high levels in cancer could increase RAC3 levels. We found that enhancement of RAC3 levels by transfection of HEK293 cells with a RAC3 expression vector induces a significant increase of cell proliferation not only in the presence, but also in the absence of serum growth factors. Moreover, the cells were transformed showing an anchorage independent growth, similar to that observed in tumoral cells. The treatment of HEK293 cells with TNF-a induced an increase in the protein levels of RAC3 and this was blocked by an NF-kB specific inhibitor, suggesting that this transcription factor is involved in the cytokine effect. We conclude that RAC3, in addition to is anti-apoptotic action, is a transforming factor that promotes the proliferation and growth independent of anchorage, and that its levels could be elevated by the action of inflammatory cytokines that are involved in the anti-tumoral response.
authors.affiliation: Laboratorio de Biología Molecular y Apoptosis, Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires e IDIM-CONICET, Buenos Aires.
authors.forename: Cecilia V
authors.initials: CV
authors.lastname: Alvarado
authors.forename: Sabrina
authors.initials: S
authors.lastname: Micenmacher
authors.forename: Marina
authors.initials: M
authors.lastname: Ruiz Grecco
authors.forename: Maria F
authors.initials: MF
authors.lastname: Rubio
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fernandez Larrosa
authors.forename: Monica A
authors.initials: MA
authors.lastname: Costas
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D014157:Transcription Factors / Q000187:drug effects; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: C411563:RAC3 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D020744:rac GTP-Binding Proteins