[PDF][PDF] Hyperactivation of protein kinase B and ERK have discrete effects on survival, proliferation, and cytokine expression in Nf1-deficient myeloid cells
S Donovan, W See, J Bonifas, D Stokoe, KM Shannon - Cancer cell, 2002 - cell.com
S Donovan, W See, J Bonifas, D Stokoe, KM Shannon
Cancer cell, 2002•cell.comThe Nf1 tumor suppressor encodes a GTPase-activating protein for Ras. Previous work has
implicated hyperactive Ras in the aberrant growth of Nf1-deficient cells; however, there are
limited data on which effectors modulate specific phenotypes. To address this, we generated
myeloid cell lines by infecting fetal liver cells with a retrovirus encoding a truncated allele of
c-Myb. Granulocyte-macrophage colony stimulating factor (GM-CSF) promoted the survival
of wild-type Myb cells in a dose-dependent manner. By contrast, Nf1-deficient myeloid cells …
implicated hyperactive Ras in the aberrant growth of Nf1-deficient cells; however, there are
limited data on which effectors modulate specific phenotypes. To address this, we generated
myeloid cell lines by infecting fetal liver cells with a retrovirus encoding a truncated allele of
c-Myb. Granulocyte-macrophage colony stimulating factor (GM-CSF) promoted the survival
of wild-type Myb cells in a dose-dependent manner. By contrast, Nf1-deficient myeloid cells …
Abstract
The Nf1 tumor suppressor encodes a GTPase-activating protein for Ras. Previous work has implicated hyperactive Ras in the aberrant growth of Nf1-deficient cells; however, there are limited data on which effectors modulate specific phenotypes. To address this, we generated myeloid cell lines by infecting fetal liver cells with a retrovirus encoding a truncated allele of c-Myb. Granulocyte-macrophage colony stimulating factor (GM-CSF) promoted the survival of wild-type Myb cells in a dose-dependent manner. By contrast, Nf1-deficient myeloid cells deprived of growth factors, were resistant to apoptosis due to hyperactivation of the phosphoinositide-3-OH kinase/protein kinase B cascade. Nf1−/− cells also demonstrated growth factor-independent proliferation and upregulation of GM-CSF mRNA production that were dependent upon Raf/MEK/ERK signaling. These data link specific Ras effectors with discrete cellular phenotypes in Nf1-deficient cells.
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