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

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Auteur principal: Fábio L. Forti
Format: Artículo científico
Langue:en
Publié: Academia Brasileira de Ciências 2006
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author Fábio L. Forti
author_facet Fábio L. Forti
contents c-Ki-ras oncogene amplification and FGF2 signaling pathways in the mouse Y1 adrenocortical cell line Fábio L. Forti Érico T. Costa Kátia M. Rocha Miriam S. Moraes Hugo A. Armelin Multidisciplinaria (Ciencias Naturales y Exactas) ki ras ERK FGF2 adrenocortical tumor cells 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 thisgenetic lesion leads to high constitutive levels of activation of the c-Ki-Ras-GTP→PI3K→Akt signalingpathway (Forti et al. 2002). On the other hand, activation levels of another important pathway downstreamof 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 ofthe ERK1/2 pathway by FGF2. Third, c-Ki-Ras-GTP high basal levels suppress activation of the c-H-Rasonco-protein. But, Y1 cells, expressing dominant negative mutant RasN17, display a rapid and transientup-regulation of c-H-Ras-GTP upon FGF2 treatment. Elucidation of FGF2-signaling pathways in Y1 tumorcells can uncover new targets for drug development of interest in cancer therapy. 2006 artículo científico 0001-3765 https://www.redalyc.org/articulo.oa?id=32778205 en http://www.redalyc.org/revista.oa?id=327 Anais da Academia Brasileira de Ciências application/pdf Academia Brasileira de Ciências Anais da Academia Brasileira de Ciências (Brasil) Num.2 Vol.78
format Artículo científico
id redalyc_32778205
institution Redalyc
language en
publishDate 2006
publisher Academia Brasileira de Ciências
spellingShingle c-Ki-ras oncogene amplification and FGF2 signaling pathways in the mouse Y1 adrenocortical cell line
Fábio L. Forti
Multidisciplinaria (Ciencias Naturales y Exactas)
ki
ras
ERK
FGF2
adrenocortical tumor cells
c-Ki-ras oncogene amplification and FGF2 signaling pathways in the mouse Y1 adrenocortical cell line Fábio L. Forti Érico T. Costa Kátia M. Rocha Miriam S. Moraes Hugo A. Armelin Multidisciplinaria (Ciencias Naturales y Exactas) ki ras ERK FGF2 adrenocortical tumor cells 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 thisgenetic lesion leads to high constitutive levels of activation of the c-Ki-Ras-GTP→PI3K→Akt signalingpathway (Forti et al. 2002). On the other hand, activation levels of another important pathway downstreamof 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 ofthe ERK1/2 pathway by FGF2. Third, c-Ki-Ras-GTP high basal levels suppress activation of the c-H-Rasonco-protein. But, Y1 cells, expressing dominant negative mutant RasN17, display a rapid and transientup-regulation of c-H-Ras-GTP upon FGF2 treatment. Elucidation of FGF2-signaling pathways in Y1 tumorcells can uncover new targets for drug development of interest in cancer therapy. 2006 artículo científico 0001-3765 https://www.redalyc.org/articulo.oa?id=32778205 en http://www.redalyc.org/revista.oa?id=327 Anais da Academia Brasileira de Ciências application/pdf Academia Brasileira de Ciências Anais da Academia Brasileira de Ciências (Brasil) Num.2 Vol.78
title c-Ki-ras oncogene amplification and FGF2 signaling pathways in the mouse Y1 adrenocortical cell line
topic Multidisciplinaria (Ciencias Naturales y Exactas)
ki
ras
ERK
FGF2
adrenocortical tumor cells
url https://www.redalyc.org/articulo.oa?id=32778205