title: Apaf-1 and caspase-9 do not act as tumor suppressors in myc-induced lymphomagenesis or mouse embryo fibroblast transformation.
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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Scott
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: Marsden
authors.forename: Alex
authors.initials: A
authors.lastname: Egle
authors.forename: Marc
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Dobrila
authors.initials: D
authors.lastname: Nesic
authors.forename: Steve
authors.initials: S
authors.lastname: Gerondakis
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
mesh_terms: D000818:Animals; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D020169:Caspases / Q000235:genetics*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005333:Fetus; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000502:physiology / Q000637:transplantation; D015994:Incidence; D008223:Lymphoma / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011828:Radiation Chimera; D019076:Transgenes / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; C489428:Myc protein, mouse; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases