Abstract
Based on experiments with cultured fibroblasts, the apoptosis regulators caspase-9 and Apaf-1 are hypothesized to function as tumor suppressors. To investigate their in vivo role in lymphomagenesis, an IgH enhancer-driven c-myc transgene was crossed onto Apaf-1(-/-) and caspase-9(-/-) mice. Due to perinatal lethality, Emu-myc transgenic Apaf-1(-/-) or caspase-9(-/-) fetal liver cells were used to reconstitute lethally irradiated recipient mice. Surprisingly, no differences were seen in rate, incidence, or severity of lymphoma with loss of Apaf-1 or caspase-9, and Apaf-1 was not a critical determinant of anticancer drug sensitivity of c-myc-induced lymphomas. Moreover, loss of Apaf-1 did not promote oncogene-induced transformation of mouse embryo fibroblasts. Thus, Apaf-1 and caspase-9 do not suppress c-myc-induced lymphomagenesis and embryo fibroblast transformation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptotic Protease-Activating Factor 1
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Caspase 9
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Caspases / genetics*
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Cell Line, Tumor
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Cells, Cultured
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Disease Progression
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Drug Resistance, Neoplasm / genetics
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Fetus
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Hepatocytes / physiology
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Hepatocytes / transplantation
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Incidence
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Lymphoma / enzymology*
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Lymphoma / genetics
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Mice
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Mice, Knockout
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Proteins / genetics*
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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Radiation Chimera
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Transgenes / genetics
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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Apaf1 protein, mouse
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Apoptotic Protease-Activating Factor 1
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Myc protein, mouse
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Proteins
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Proto-Oncogene Proteins c-myc
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Tumor Suppressor Proteins
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Casp9 protein, mouse
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Caspase 9
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Caspases