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-l 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-l or caspase-9, and Apaf-l was not a critical determinant of anticancer drug sensitivity of c-myc-induced lymphomas. Moreover, loss of Apaf-l did not promote oncogene-induced transformation of mouse embryo fibroblasts. Thus, Apaf-l and caspase-9 do not suppress c-myc-induced lymphomagenesis and embryo fibroblast transformation.