title: c-Ki-ras oncogene amplification and FGF2 signaling pathways in the mouse Y1 adrenocortical cell line.
abstract: 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.
authors.affiliation: Instituto de Química, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil.
authors.forename: Fábio L
authors.initials: FL
authors.lastname: Forti
authors.forename: Erico T
authors.initials: ET
authors.lastname: Costa
authors.forename: Kátia M
authors.initials: KM
authors.lastname: Rocha
authors.forename: Miriam S
authors.initials: MS
authors.lastname: Moraes
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Armelin
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D051379:Mice; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D016222:Fibroblast Growth Factor 2