Comparison of the anti-apoptotic effects of Bcr-Abl, Bcl-2 and Bcl-x(L) following diverse apoptogenic stimuli.
Ectopic expression of Bcr-Abl, Bcl-2 or Bcl-x(L) in HL-60 cells conferred resistance to apoptosis against a variety of death-inducing agents. Bcr-Abl-mediated interference with mitochondrial events was confirmed by the analysis of the loss of mitochondrial transmembrane potential and cytochrome c release. HL-60.Bcr-Abl cells were extremely resistant to all apoptogenic stimuli tested, even in circumstances where HL-60.Bcl-2 or HL-60.Bcl-x(L) cells were only partially protected from apoptosis. The levels of Mcl-1, Bax, Bid, Akt, c-IAP-1, c-IAP-2, XIAP and c-FLIP were compared in all HL-60 lines. Our findings show that Bcr-Abl is a more powerful anti-apoptotic molecule than Bcl-2 or Bcl-x(L).
Brumatti
Gabriela
G
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Brazil.
Weinlich
Ricardo
R
Chehab
Cristina F
CF
Yon
Monica
M
Amarante-Mendes
Gustavo P
GP
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D018432:Drug Resistance, Multiple; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D010718:Phosphatidylserines / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D016044:Fusion Proteins, bcr-abl; D020169:Caspases