Cutting edge: TRAIL deficiency accelerates hematological malignancies.
TNF apoptosis-inducing ligand is attracting considerable interest as a potential extrinsic tumor suppressor mechanism, although previous reports have conveyed somewhat contrasting views regarding the likely importance of this pathway. In this study, we provide the first evaluation of spontaneous tumor formation over the life span of TRAIL-deficient mice. Interestingly, >25% of these mice do develop lymphoid malignancies after 500 days of life. TRAIL suppressed the initiation and development of both tumors of lymphoid and stromal origin in the context of the loss of at least one p53 allele. Specific examination of the role of TRAIL in Her2/neu oncogene-driven mammary epithelial cancer revealed no critical role for TRAIL despite the inherent TRAIL sensitivity of such mammary carcinomas. Overall, the data indicate an important function of TRAIL in controlling carcinogenesis, but suggest that further examination of this pathway in epithelial malignancies is warranted.
Zerafa
Nadeen
N
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Westwood
Jennifer A
JA
Cretney
Erika
E
Mitchell
Sally
S
Waring
Paul
P
Iezzi
Manuela
M
Smyth
Mark J
MJ
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000502:physiology*; D018734:Genes, erbB-2; D016158:Genes, p53; D019337:Hematologic Neoplasms / Q000209:etiology*; D008223:Lymphoma / Q000209:etiology / Q000517:prevention & control; D015674:Mammary Neoplasms, Animal / Q000209:etiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha