BCR/ABL confers growth factor independence upon a murine myeloid cell line.
The BCR/ABL oncogene in chronic myelogenous leukemia produces an activated tyrosine kinase fusion protein (p210). Like other tyrosine kinase oncogenes, BCR/ABL can abrogate the interleukin-3 (IL-3) dependence of lymphoid cell lines. To investigate the ability of BCR/ABL to generate growth factor independence in myeloid cells, the IL-3 dependent myeloid cell line NFS/N1.H7 (H7) was transfected with the p210BCR/ABL-containing plasmid, pGD210. Stable clones A54 and A74 were capable of IL-3 independent growth and tumor formation in syngeneic mice. Relief of growth factor dependence was not mediated by autocrine release of IL-3. The baseline proliferation rate of the BCR/ABL transformed cells was greater than that of the parental H7 cells maximally stimulated by IL-3. Abundant constitutive expression of c-myc, c-jun, and c-fos was observed in the p210BCR/ABL transfectants even in low serum conditions. In contrast, c-myc expression in H7 cells was dependent upon IL-3 stimulation, and neither c-jun nor c-fos was highly expressed following IL-3 stimulation in H7 cells. Thus, BCR/ABL transformation and relief of IL-3 dependence involve not only pathways that can substitute for IL-3 induced growth via tyrosine kinase mediated signals, but also pathways that recruit constitutive c-jun and c-fos expression.
Mandanas
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Department of Medicine, Indiana University School of Medicine, Indianpolis.
Boswell
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Leibowitz
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D000818:Animals; D002455:Cell Division / Q000235:genetics; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D015870:Gene Expression; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007377:Interleukin-3 / Q000502:physiology; D051379:Mice; D009857:Oncogenes / Q000502:physiology*; D011061:Poly A / Q000032:analysis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger; D015398:Signal Transduction
D007377:Interleukin-3; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA