Coordinate expression loss of <i>GKN1</i> and <i>GKN2</i> in gastric cancer via impairment of a glucocorticoid-responsive enhancer
Sharleen Chung Nien Chin, Louise O’Connor, Michelle Scurr, Jonathan T. Busada, Alison Graham, Ghazal Alipour Talesh, Chau P. Tran, Sohinee Sarkar, Toshinari Minamoto, Andrew S. Giraud, John A. Cidlowski, Philip Sutton, Trevelyan R. Menheniott
Abstract
Gastrokine 2 (GKN2) is an anti-inflammatory protein produced by the gastric epithelium. GKN2 expression is progressively lost during gastric cancer (GC), which is believed to play a casual role in GC development. Here, we use bacterial artificial chromosome transgenic studies to identify a glucocorticoid-responsive enhancer element that likely governs expression of GKN1/GKN2, which, via parallel expression loss of the anti-inflammatory glucocorticoid receptor, reveals a novel mechanism to explain the loss of GKN2 during GC pathogenesis.