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Ablation of TNF or lymphotoxin signaling and the frequency of spontaneous tumors in p53-deficient mice

Item Type:Article
Title:Ablation of TNF or lymphotoxin signaling and the frequency of spontaneous tumors in p53-deficient mice
Creators Name:Kuprash, D.V. and Qin, Z. and Ito, D. and Grivennikov, S.I. and Abe, K. and Drutskaya, L.N. and Blankenstein, T. and Nedospasov, S.A.
Abstract:TNF plays diverse and contrasting roles in cancer, promoting skin carcinogenesis and metastasis, but also possessing potent antitumor effects in mice. TNF via TNFR1 axis induces NFkappaB, and may contribute to inflammation-facilitated neoplasia. On the other hand, lymphomas are cited as rare complications of anti-TNF therapy in humans. In order to address possible modulating role of TNF and of a related cytokine, LTalpha, in spontaneous tumorigenesis, we compared mice with p53-TNF, p53-LTalpha, p53-TNFR1 and p53-TNF-LT combined deficiencies. Unexpectedly, neither of these mice showed significant modulation of their survival or shift in the spectrum of emerging tumors, as compared to p53-deficient mice, arguing against direct link between TNF blockade and lymphoma development.
Keywords:Cytokine and Chemokine Biology, p53/mdm2, Tumor Immunology, Knockout Mice, p53 Genes, Inflammation, Lymphoma, Lymphotoxin-alpha, Inbred C57BL Mice, Type I Tumor Necrosis Factor Receptors, Signal Transduction, Survival Analysis, Tumor Necrosis Factor-alpha, Animals, Mice
Source:Cancer Letters
ISSN:0304-3835
Publisher:Elsevier (The Netherlands)
Volume:268
Number:1
Page Range:70-75
Date:8 September 2008
Official Publication:https://doi.org/10.1016/j.canlet.2008.03.023
PubMed:View item in PubMed

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