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Cell Growth & Differentiation, Vol 7, Issue 9 1141-1148, Copyright © 1996 by American Association of Cancer Research


ARTICLES

Isoform-specific functions of c-abl: type I is necessary for differentiation, and type IV is inhibitory to apoptosis

R Daniel, PM Wong and SW Chung
Fels Institute for Cancer Research and Molecular Biology, Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.

The c-abl proto-oncogene is expressed ubiquitously during development. There are two predominant isoforms, type I and type IV. Their biological functions in cell growth and development are unknown. To examine their respective biological roles, we transduced 70Z/3 lymphoid cells with antisense sequences specific to each respective isotype. When the cells were incubated with antisense oligonucleotides against type IV c-abl but not against type I c-abl, induction of apoptosis was observed, as measured by either DNA fragmentation, cell proliferation, or colony formation. Immunoprecipitation showed that antisense-treated cells had reduced amounts of c-abl as compared to the untreated cells. When stimulated with lipopolysaccharide (LPS), 70Z/3 cells underwent proliferation and differentiation. When antisense oligonucleotides against type IV were added to the cell cultures, with LPS stimulation, induction of apoptosis continued to occur. When antisense oligonucleotides against type I were added in the cultures, in the presence of LPS, cell differentiation was inhibited, but cell proliferation continued to occur. This inhibition of differentiation was evident by a lack of immunoglobulin light chain production by cells that otherwise would produce immunoglobulin when they are stimulated with LPS. These data therefore show that type I c-abl allows cell differentiation to occur, whereas type IV c-abl suppresses apoptosis.


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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1996 by the American Association of Cancer Research.