c-Ki-ras oncogene amplification and FGF2 signaling pathways in the mouse Y1 adrenocortical cell line

• Autor(a) principal: Forti,Fábio L.
• Data de Publicação: 2006
• Outros Autores: Costa,Érico T., Rocha,Kátia M., Moraes,Miriam S., Armelin,Hugo A.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Anais da Academia Brasileira de Ciências (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652006000200005
• topic: FGF2; adrenocortical tumor cells; c-ki-ras; c-h-ras; ERK

The mouse Y1 adrenocortical tumor cell line is highly responsive to FGF2-(Fibroblast Growth Factor 2) and possesses amplified and over-expressed c-Ki-ras proto-oncogene. We previously reported that this genetic lesion leads to high constitutive levels of activation of the c-Ki-Ras-GTP->PI3K->Akt signaling pathway (Forti et al. 2002). On the other hand, activation levels of another important pathway downstream of c-Ki-Ras-GTP, namely, Raf->MEK->ERK, remain strictly dependent on FGF2 stimulation (Rocha et al. 2003). Here we show that, first, FGF2 transiently up-regulates the c-Ki-Ras-GTP->PI3K->Akt pathway, in spite of its high basal levels. Second, c-Ki-Ras-GTP transient up-regulation likely underlies activation of the ERK1/2 pathway by FGF2. Third, c-Ki-Ras-GTP high basal levels suppress activation of the c-H-Ras onco-protein. But, Y1 cells, expressing dominant negative mutant RasN17, display a rapid and transient up-regulation of c-H-Ras-GTP upon FGF2 treatment. Elucidation of FGF2-signaling pathways in Y1 tumor cells can uncover new targets for drug development of interest in cancer therapy.