Congresos y reuniones científicas
Título:
KLF6 Tumor Suppressor is Induced Upon Expression of Activated RAS: Anti-Oncogenesis or Oncogenesis ?
Autor/es:
TRUCCO LD; ANDREOLI V; BOCCO JL
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.