Tumorigenic Activity of the BCR-ABL Oncogenes is Mediated by BCL2

BCR-ABL is a chimeric oncogene generated by translocation of sequences from the c-abl protein-tyrosine kinase gene on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, p210BCR-ABLand p190BCR-ABL, are produced that are characteristic of chronic myelogenous leukemia and a...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-06, Vol.92 (12), p.5287-5291
Main Authors: Sanchez-Garcia, I., Grutz, G.
Format: Article
Language:English
Subjects:
Abl gene
Animals
Apoptosis
Apoptosis - genetics
Bcl-2 gene
bcl-abl protein
Bcr gene
Biochemistry
c-abl protein
c-myc gene
Cell culture techniques
Cell growth
Cell Line
Cell lines
Cell Transformation, Neoplastic - genetics
chromosome 9
Fusion Proteins, bcr-abl - genetics
Humans
interleukin 3
Interleukin-3 - pharmacology
K562 cells
Leukemia
Male
man
Medical research
Mice
Mice, Nude
Oncogenes
Oxidative Stress
p190 bcr-abl protein
Philadelphia chromosome
Plasmids
protein-tyrosine kinase
Protein-Tyrosine Kinases - genetics
Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-bcl-2
Transfection
Transformed cell line
Tumor cell line
tumors
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Description
Summary:BCR-ABL is a chimeric oncogene generated by translocation of sequences from the c-abl protein-tyrosine kinase gene on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, p210BCR-ABLand p190BCR-ABL, are produced that are characteristic of chronic myelogenous leukemia and acute lymphoblastic leukemia, respectively. Their role in the etiology of human leukemia remains to be defined. Transformed murine hematopoietic cells can be used as a model of BCR-ABL function since these cells can be made growth factor independent and tumorigenic by the action of the BCR-ABL oncogene. We show that the BCR-ABL oncogenes prevent apoptotic death in these cells by inducing a Bcl-2 expression pathway. Furthermore, BCR-ABL-expressing cells revert to factor dependence and nontumorigenicity after Bcl-2 expression is suppressed. These results help to explain the ability of BCR-ABL oncogenes to synergize with c-myc in cell transformation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.12.5287