Induction of Apoptosis by a Dominant Negative H-RAS Mutant (116Y) in K562 Cells

Bcl-2-independent Bcr–Abl-mediated resistance to apoptosis: protection is correlated with up regulation of Bcl-xL

“…Therefore, other signals probably also contribute to the Bcr ± Ablmediated anti-apoptotic phenotype. One possible candidate is the oncogene Ras, which was shown to be important in Bcr ± Abl-mediated transformation (Pendergast et al, 1993) and also to participate in the resistance to apoptosis observed in the CML line K562 (Sakai et al, 1994) and more recently in 32D.Bcr ± Abl cells (Cortez et al, 1996). The fact that Bcr ± Abl modulated the expression of Bcl-x L in other cell types suggests a common anti-apoptotic pathway initiated by Bcr ± Abl.…”

BCR – ABL activates pathways mediating cytokine independence and protection against apoptosis in murine hematopoietic cells in a dose-dependent manner

“…We reasoned that this latter construct might lead to a lower expression level more closely approximating that of BCR ± ABL in chronic phase CML. We extended our studies to include cell lines expressing a constitutively activated ras oncogene or a dominant-negative ras, since it has been argued that activation of the ras/MAPK pathway is important in BCR ± ABL-mediated transformation and resistance to apoptosis (Pendergast et al, 1993;Sakai et al, 1994;Cortez et al, 1995Cortez et al, , 1996Goga et al, 1995;Raitano et al, 1995;Sawyers et al, 1995).…”

BCR/ABL: from molecular mechanisms of leukemia induction to treatment of chronic myelogenous leukemia

“…Inhibition of RAS signaling by expression of dominant-negative RAS, blockage of Grb2 adaptor protein function or incubation with antisense oligonucleotides to p21Ras, prevents BCR/ABL transformation in several cell line models (Gishizky et al, 1995;Sawyers et al, 1995;Sakai et al, 1994;Skorski et al, 1994a). Ras function depends on proper subcellular localization at the plasma membrane through addition of a 15-carbon farnesyl group to Ras, a reaction that is catalysed by the farnesyl protein transferase (FPT) enzyme (Gutierrez et al, 1989;Hancock et al, 1989;Long et al, 2001;Reiss et al, 1990;Stokoe et al, 1994).…”