Journal article

Loss of NFKB1 Results in Expression of Tumor Necrosis Factor and Activation of Signal Transducer and Activator of Transcription 1 to Promote Gastric Tumorigenesis in Mice

Jun T Low, Michael Christie, Matthias Ernst, Laure Dumoutier, Adele Preaudet, Yanhong Ni, Michael DW Griffin, Lisa A Mielke, Andreas Strasser, Tracy L Putoczki, Lorraine A O'Reilly



BACKGROUND & AIMS: Activity of nuclear factor κB transcription factors and signaling via signal transducer and activator of transcription (STAT) are frequently altered in gastric cancer cells. Mice lacking NFKB1 (Nfkb1-/- mice) develop invasive gastric cancer, and their gastric tissues have increased levels of cytokines, such as interleukin (IL) 6, IL22, IL11, and tumor necrosis factor (TNF), as well as increased activation of STAT1. We investigated whether these cytokines were required for STAT1 activation in gastric tissues of mice and critical for gastric tumorigenesis. METHODS: We crossed Nfkb1-/- mice with Il6-/-, Il22-/-, Il11Rα-/-, and Tnf-/- mice. Stomach tissues from compound mutant..

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Awarded by Cancer Council Victoria

Awarded by Cancer Council New South Wales project

Awarded by Cancer Council NSW (Box Rallies)

Awarded by National Health and Medical Research Council, Canberra

Awarded by Victorian Cancer Agency Fellowship

Awarded by Worldwide Cancer Research project

Awarded by NHMRC infrastructure grant

Awarded by Leukemia and Lymphoma Society

Awarded by Juvenile Diabetes Research Foundation/National Health and Medical Research Council

Funding Acknowledgements

This work was supported by a Cancer Council Victoria Grant-in-Aid project grant 1161400 (to Lorraine A. O'Reilly, Andreas Strasser, Tracy Putoczki, and Matthias Ernst) a Cancer Australia and Cancer Council New South Wales project grant 1047672 (to Lorraine A. O'Reilly, Tracy Putoczki, Andreas Strasser, and Matthias Ernst) and, a Cancer Council NSW (Box Rallies) RG 20-13 (to Lorraine A. O'Reilly, Tracy Putoczki, Michael Christie, Matthias Ernst). Additional support included fellowships and grants from the National Health and Medical Research Council, Canberra, program 1016701 (Andreas Strasser), fellowship; 1020363 (Andreas Strasser) and project grants; 1046010 (Andreas Strasser); 1008614, 1080498 (Tracy Putoczki); The Walter and Eliza Hall Institute of Medical Research Dyson Bequest Centenary Fellowship (Tracy Putoczki), Victorian Cancer Agency Fellowship MCRF16009 (Tracy Putoczki), Worldwide Cancer Research project grant 14-1197 (Tracy Putoczki), Australian Postgraduate Award (Jun Ting Low), TopUp Scholarship, Cancer Therapeutics CRC (Australia; Jun Ting Low) and an NHMRC infrastructure grant, Independent Research Institutes Infrastructure Support Scheme grant 361646, the Victorian State Government (Operational Infrastructure Support Program grant), the Leukemia and Lymphoma Society (grant 7413 and 7001-13) and the Juvenile Diabetes Research Foundation/National Health and Medical Research Council 466658 (Andreas Strasser).