Apaf-1 and caspase-9 do not act as tumor suppressors in myc-induced lymphomagenesis or mouse embryo fibroblast transformation.
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.
Scott
Clare L
CL
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Schuler
Martin
M
Marsden
Vanessa S
VS
Egle
Alex
A
Pellegrini
Marc
M
Nesic
Dobrila
D
Gerondakis
Steve
S
Nutt
Stephen L
SL
Green
Douglas R
DR
Strasser
Andreas
A
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*
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