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Title: The molecular pathogenesis of STAT3-driven gastric tumourigenesis in mice is independent of IL-17
Authors: Kennedy, C.L.
Najdovska, M.
Jones, G.W.
McLeod, L.
Hughes, N.R.
Allison, C.
Huey Ooi, C. 
Tan, P. 
Ferrero, R.L.
Jones, S.A.
Dev, A.
Sievert, W.
Bhathal, P.S.
Jenkins, B.J.
Keywords: gastric cancer
Issue Date: Oct-2011
Citation: Kennedy, C.L., Najdovska, M., Jones, G.W., McLeod, L., Hughes, N.R., Allison, C., Huey Ooi, C., Tan, P., Ferrero, R.L., Jones, S.A., Dev, A., Sievert, W., Bhathal, P.S., Jenkins, B.J. (2011-10). The molecular pathogenesis of STAT3-driven gastric tumourigenesis in mice is independent of IL-17. Journal of Pathology 225 (2) : 255-264. ScholarBank@NUS Repository.
Abstract: Chronic activation of the gastric mucosal adaptive immune response is a characteristic trait of gastric cancer. It has recently emerged that a new class of T helper (Th) cells, defined by their ability to produce interleukin (IL)-17A (Th17), is associated with a host of inflammatory responses, including gastritis. However, the role of these Th17 cells in the pathogenesis of gastric cancer is less clear. To formally address this, we employed gp130F/F mice, which spontaneously develop gastric inflammation-associated tumours akin to human intestinal-type gastric cancer. At the molecular level, these tumours demonstrate hyper-activation of the latent transcription factor signal transducer and activator of transcription (STAT)3 via the IL-6 cytokine family member, IL-11. In gp130F/F mice, the generation of Th17 cells, as well as the gastric expression of IL-17a and other Th17-related factors (Rorγt, IL-23), were augmented compared to wild-type gp130+/+ mice. Consistent with a role for IL-6 and STAT3 in regulating IL-17A, increased Th17 generation and gastric expression of Th17-related factors in gp130 F/F mice were reduced to wild-type levels in gp130 F/F:Stat3-/+ mice displaying normalized STAT3 activity, and also in gp130F/F:IL-6-/- mice. Importantly, genetic ablation of IL-17A in gp130F/F:IL-17a-/- mice did not suppress the initiation and growth of gastric tumours. Furthermore, IL-17A and RORC gene expression was strongly increased in human gastric biopsies from patients with gastritis, but not gastric cancer. Collectively, our data suggest that increased expression of Th17-related factors does not correlate with the molecular pathogenesis of gastric tumourigenesis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Copyright © 2011 Pathological Society of Great Britain and Ireland.
Source Title: Journal of Pathology
ISSN: 00223417
DOI: 10.1002/path.2933
Appears in Collections:Staff Publications

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