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Apaf-1 and caspase-9 do not act as tumor suppressors in myc-induced lymphomagenesis or mouse embryo fibroblast transformation.

Scott CL, Schuler M, Marsden VS, Egle A, Pellegrini M, Nesic D, Gerondakis S, Nutt SL, Green DR, Strasser A - J. Cell Biol. (2004)

Bottom Line: Based on experiments with cultured fibroblasts, the apoptosis regulators caspase-9 and Apaf-1 are hypothesized to function as tumor suppressors.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.Thus, Apaf-1 and caspase-9 do not suppress c-myc-induced lymphomagenesis and embryo fibroblast transformation.

View Article: PubMed Central - PubMed

Affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.

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.

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Hematologic parameters of mice with lymphoma. (A) Total peripheral blood white cell count from mice with lymphoma at time of sacrifice. (B) Spleen weight from mice with lymphoma. Data represent arithmetic means ± SD of 3–12 mice of each genotype.
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fig2: Hematologic parameters of mice with lymphoma. (A) Total peripheral blood white cell count from mice with lymphoma at time of sacrifice. (B) Spleen weight from mice with lymphoma. Data represent arithmetic means ± SD of 3–12 mice of each genotype.

Mentions: No differences were seen with the loss of Apaf-1 in the severity of Eμ-myc lymphoma, as determined by peripheral blood lymphocytosis or spleen size. An increase in leukemic transformation was seen more frequently in mice with Bcl-2 overexpression although the splenomegaly was similar in all genotypes (Fig. 2). The severity of multi-organ involvement by lymphoma was determined by histologic analysis of bone marrow, spleen, lymph nodes, liver, lung, kidney, and heart (scored blinded as to genotype of section), and no increase in severity was observed for either the heterozygote or homozygote deficiency for either Apaf-1 or caspase-9 (unpublished data).


Apaf-1 and caspase-9 do not act as tumor suppressors in myc-induced lymphomagenesis or mouse embryo fibroblast transformation.

Scott CL, Schuler M, Marsden VS, Egle A, Pellegrini M, Nesic D, Gerondakis S, Nutt SL, Green DR, Strasser A - J. Cell Biol. (2004)

Hematologic parameters of mice with lymphoma. (A) Total peripheral blood white cell count from mice with lymphoma at time of sacrifice. (B) Spleen weight from mice with lymphoma. Data represent arithmetic means ± SD of 3–12 mice of each genotype.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171953&req=5

fig2: Hematologic parameters of mice with lymphoma. (A) Total peripheral blood white cell count from mice with lymphoma at time of sacrifice. (B) Spleen weight from mice with lymphoma. Data represent arithmetic means ± SD of 3–12 mice of each genotype.
Mentions: No differences were seen with the loss of Apaf-1 in the severity of Eμ-myc lymphoma, as determined by peripheral blood lymphocytosis or spleen size. An increase in leukemic transformation was seen more frequently in mice with Bcl-2 overexpression although the splenomegaly was similar in all genotypes (Fig. 2). The severity of multi-organ involvement by lymphoma was determined by histologic analysis of bone marrow, spleen, lymph nodes, liver, lung, kidney, and heart (scored blinded as to genotype of section), and no increase in severity was observed for either the heterozygote or homozygote deficiency for either Apaf-1 or caspase-9 (unpublished data).

Bottom Line: Based on experiments with cultured fibroblasts, the apoptosis regulators caspase-9 and Apaf-1 are hypothesized to function as tumor suppressors.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.Thus, Apaf-1 and caspase-9 do not suppress c-myc-induced lymphomagenesis and embryo fibroblast transformation.

View Article: PubMed Central - PubMed

Affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.

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.

Show MeSH
Related in: MedlinePlus