INVESTIGADORES
LOPEZ BERGAMI Pablo Roberto
congresos y reuniones científicas
Título:
STAT3 Regulates PDK1 Expression and Akt Activity in Melanoma.
Autor/es:
MARIA ELISA PICCO; MARIA SOL BRAVO; DAIANA MARTIRE GRECO; NATALIA FERNANDEZ; HYUNGSOO KIM; ZEEV RONAI; PABLO LOPEZ BERGAMI
Lugar:
Boston
Reunión:
Congreso; Sixth International Melanoma Research Congress; 2009
Institución organizadora:
Society for Melanoma Research
Resumen:
The failure of targeted therapies attempted in melanoma indicates that a
more profound understanding of its altered signaling pathways and
particularly the interplay among them, is required. The PI3K/Akt and the
JAK/STAT3 pathways are activated in melanoma and are usually depicted
as parallel paths to oncogenesis. The evidence showing a link between
them is scarce or controversial. In the present work we studied the
regulation of the expression of Phosphoinositide-Dependent Kinase-1
(PDK1), a master kinase involved in Akt phosphorylation and activation,
by STAT3. Expression of dominant negative STAT3 constructs STAT3β and
STAT3Y as well as siRNA against STAT3 inhibited both PDK1 mRNA and
protein levels. Serial deletions of the 5′ region of the PDK1 promoter
allowed to map two functional STAT3 responsive elements at −265 and −130
of the PDK1 promoter. STAT3-dependent transcription of PDK1 was
abolished by mutations that simultaneously destroy both elements. The
reduction on PDK1 expression following STAT3 inhibition resulted in an
weakend Akt phosphorylation and activity. These results indicate that
constitutive activation of STAT3 contributes to Akt activity through
upregulation of PDK1 expression.