Overexpression of IL-11 promotes premalignant gastric epithelial hyperplasia in isolation from germline gp130-JAK-STAT driver mutations
Jon N Buzzelli, Louise O'Connor, Michelle Scurr, Sharleen Chung Nien Chin, Angelique Catubig, Garrett Z Ng, Masanobu Oshima, Hiroko Oshima, Andrew S Giraud, Philip Sutton, Louise M Judd, Trevelyan R Menheniott
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | AMER PHYSIOLOGICAL SOC | Published : 2019
Expression of the cytokine IL-11 is elevated in human Helicobacter pylori infection and progressively increases with worsening gastric pathology. Additionally, IL-11 is required for tumor development in STAT3-dependent murine models of gastric cancer (GC) and, when administered acutely, causes resolving atrophic gastritis. However, it is unclear whether locally elevated IL-11 ligand expression can, in isolation from oncogenic gp130-JAK-STAT pathway mutations, initiate GC pathogenesis. Here we developed a transgenic mouse model of stomach-specific (keratin 19 promoter) IL-11 ligand overexpression. Keratin 19 promoter-IL-11 transgenic ( K19-IL11Tg) mice showed specific IL-11 overexpression in ..View full abstract
Awarded by National Health and Medical Research Council of Australia
This study was supported by a research project grant (1006688, to L. M. Judd) and by fellowships 1026674 (to T. R. Menheniott), 1008776 (to L. M. Judd), 607330 (to A. S. Giraud), and 1020387 (to P. Sutton) from the National Health and Medical Research Council of Australia and Victorian Government's Medical Research Operational Infrastructure Support Program.