Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer
Sharleen Chung Nien Chin, Louise O'Connor, Michelle Scurr, Jonathan T Busada, Alison N Graham, Ghazal Alipour Talesh, Chau P Tran, Sohinee Sarkar, Toshinari Minamoto, Andrew S Giraud, John A Cidlowski, Philip Sutton, Trevelyan R Menheniott
American Journal of Physiology-Gastrointestinal and Liver Physiology | AMER PHYSIOLOGICAL SOC | Published : 2020
Gastrokines (GKNs) are anti-inflammatory proteins secreted by gastric epithelial (surface mucous and pit) cells, with their aberrant loss of expression causally linked to premalignant inflammation and gastric cancer (GC). Transcriptional mechanisms accounting for GKN expression loss have not been elucidated. Using human clinical cohorts, mouse transgenics, bioinformatics, and transfection/reporter assays, we report a novel mechanism of GKN gene transcriptional regulation and its impairment in GC. GKN1/GKN2 loss is highly coordinated, with both genes showing parallel downregulation during human and mouse GC development, suggesting joint transcriptional control. In BAC transgenic studies, we d..View full abstract
Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by NHMRC
This study was supported by a project grant (1047208) from the National Health and Medical Research Council (NHMRC) of Australia; a NHMRC Career Development Fellowship awarded to T. R. Menheniott (1026674) and further supported by the Victoria Government's Medical Research Operational Infrastructure Support Program.