Genetic ablation of Tnfα demonstrates no detectable suppressive effect on inflammation-related mouse colon tumorigenesis

Hiroyasu Sakai, Yasuhiro Yamada, Masahito Shimizu, Kuniaki Saito, Hisataka Moriwaki, Akira Hara

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Colorectal cancer (CRC) is one of the most serious complications of inflammatory bowel disease. Tumor necrosis factor-α (Tnfα) is a major mediator of inflammation and there is increasing evidence that Tnfα/Tnf-receptor-1 (Tnfr1) signaling may act as an endogenous tumor promoter for colon carcinogenesis. In fact, a previous study revealed that mice lacking Tnfr1 develop significantly fewer colonic tumors in the inflammation-related CRC model. In addition, antibodies against Tnfα have been shown to inhibit the development of inflammation-related CRC. In the present study, Apc Min/+; Tnfα -/- mice were treated with 2% dextran sodium sulfate (DSS) and the tumor development was compared with Apc Min/+; Tnfα +/+ control mice in order to investigate the role of Tnfα by itself in the inflammation-related CRC. Surprisingly, there were no detectable differences in either the severity of colonic inflammation or the expression of DSS-induced chemokines and cytokines (Ccl2, Cxcl1, Tnfβ, Il1 β, Il6, and Cox-2) that relate to the colonic inflammation and tumorigenesis between these two groups. Furthermore, the genetic ablation of Tnfα did not suppress the colon tumorigenesis in comparison to the wild-type mice. Our observations suggest that intricate inflammatory responses promote the inflammation-related mouse colon tumorigenesis.

Original languageEnglish
Pages (from-to)423-430
Number of pages8
JournalChemico-Biological Interactions
Issue number3
Publication statusPublished - 03-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Toxicology


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