Isolation and characterization of an apoptosis-resistant variant of human leukemia HL-60 cells that has switched expression from Bcl-2 to Bcl-XL

• Published in: Cancer research (Chicago, Ill.) Ill.), 1996-04, Vol.56 (7), p.1621-1628
• Main Authors: ZHIYONG HAN, DEVASIS CHATTERJEE, EARLY, J, PANTAZIS, P, HENDRICKSON, E. A, WYCHE, J. H
• Format: Article
• Language: English
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Ageing, cell death; Alkaloids - pharmacology; Apoptosis; Base Sequence; bcl-2-Associated X Protein; bcl-X Protein; Biological and medical sciences; Cell physiology; Cycloheximide - pharmacology; Fundamental and applied biological sciences. Psychology; HL-60 Cells - chemistry; Humans; Molecular and cellular biology; Molecular Sequence Data; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins c-bcl-2; Staurosporine
• ISSN: 0008-5472; 1538-7445

Human promyelocytic leukemia HL-60 cells treated with 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) undergo growth arrest and subsequently die by apoptosis. We describe here the isolation of a variant of HL-60 cells, HCW-2, which was resistant to the cytotoxic effects of 8-Cl-cAMP, but still underwent growth arrest. Thus, HCW-2 cells appeared to be altered in their ability to undergo apoptosis. HCW-2 cells were also completely refractory to the apoptotic action of cycloheximide and staurosporine, two compounds which were very potent inducers of apoptosis in the parental HL-60 cells, suggesting that the resistance to apoptosis was not unique to 8-Cl-cAMP. Western blot analysis demonstrated that the parental HL-60 cells expressed both Bcl-2 and Bax, two factors known to be intimately involved in the control of apoptosis. Surprisingly, HCW-2 cells no longer expressed Bcl-2 protein and paradoxically contained Bax protein at a level that was approximately 50-fold higher than in HL-60 cells. However, Northern and Western analyses indicated that the apoptotic suppressor gene, bcl-xL, which is not expressed in the parental HL-60 cells, was expressed in HCW-2 cells. Thus, the Bcl-2-independent resistance of HCW-2 cells to apoptotic induction is discussed in terms of the expression of bcl-xL.