Artículo
Krüppel-like factor 6 interferes with cellular transformation induced by the H- ras oncogene
Trucco, Lucas Daniel
; Andreoli, Veronica
; Nuñez, Nicolás Gonzalo; Maccioni, Mariana
; Bocco, Jose Luis
Fecha de publicación:
12/2014
Editorial:
Federation of American Societies for Experimental Biology
Revista:
FASEB Journal
ISSN:
0892-6638
e-ISSN:
1530-6860
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
KLF6 is a member of the Krüppel-like factor family of transcription factors with diverse roles in the regulation of cell physiology including proliferation, signal transduction, and apoptosis. Mutations or downregulation of klf6 have been described in several human cancers. In this work, we found that KLF6 knockdown resulted in the formation of transformed foci and allowed the spontaneous conversion of NIH3T3 cells to a tumorigenic state. We further assessed the role of KLF6 in the context of oncogenic Ras expression. KLF6 expression was up-regulated in cells expressing H-RasG12V in a Jun N-terminal Kinase-dependent manner, correlated with enhanced klf6 promoter activity. We also demonstrate that ectopic KLF6 expression induced a G1-phase cell cycle arrest, thereby decreasing cell proliferation rate. Additionally, constitutive KLF6 expression impaired H-RasG12V-mediated loss of density-dependent growth inhibition and anchorage-independent growth. Moreover, stably KLF6 expression reduced tumor growth in mice challenged with cells expressing H-RasG12V. KLF6 expression correlated with up-regulation of p21, whereas neither p53 induction nor apoptotic cell death was detected. Further, p21 knockdown impaired KLF6-induced G1 cell cycle arrest. These findings provide novel evidence highlighting KLF6 function in response to malignant transformation, suggesting a relevant activity of KLF6 in controlling cell proliferation and hindering tumorigenesis.
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Articulos(CCT - CORDOBA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Trucco, Lucas Daniel; Andreoli, Veronica; Nuñez, Nicolás Gonzalo; Maccioni, Mariana; Bocco, Jose Luis; Krüppel-like factor 6 interferes with cellular transformation induced by the H- ras oncogene; Federation of American Societies for Experimental Biology; FASEB Journal; 28; 12; 12-2014; 5262-5276
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