CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
KLF6 Tumor Suppressor is Induced Upon Expression of Activated RAS: Anti-Oncogenesis or Oncogenesis ?
Autor/es:
TRUCCO L.D.; ANDREOLI V. ; BOCCO J.L.
Lugar:
Potrero de Los Funes. San Luis
Reunión:
Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011
Institución organizadora:
SAIB
Resumen:
KLF6 is a member of the Krüppel-like factor family of transcriptional regulators and a tumor suppressor gene whose loss of expression or activity, due to loss-of-heterozygocity LOH, mutation, or promoter methylation, occur in many types of cancer. We demonstrated that this protein interacts with the c-Jun oncoprotein and induces its degradation leading to inhibition of cell proliferation. c-Jun is a major component of the AP-1 transcription factor, an important cooperating partner of oncogenic Ras in cell transformation, which also requires the function of Jun N-terminal Kinases (JNKs). This work focuses on biochemical and molecular mechanisms involving KLF6 as a factor that could regulate the oncogenic activation triggered by the Ras pathway. To investigate a possible Ras-KLF6 crosstalk, we took advantage of a Ras-inducible model. We stable transduced NIH3T3 fibroblasts to express a constitutively active H-Ras (G12V) under the control of a tetracycline inducible promoter. Here we demonstrate that HRasG12V induction leads to a progressive increase of KLF6 protein in a time-dependent manner. This KLF6 increase can be repressed by a JNKs specific inhibitor. Further, in experiments where KLF6 is over expressed after Ras induction we observed a decrease in cell proliferation rate. Thus, results are consistent with the ability of KLF6 to impair enhanced cell proliferation following activation of Ras oncogene.