Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.

Gasdermin (GSDM or GSDMA), expressed in the upper gastrointestinal tract but frequently silenced in gastric cancers (GCs), regulates apoptosis of the gastric epithelium. It has three human homologs, GSDMB, GSDMC, and GSDMD (GSDM family) and they are considered to be involved in the regulation of epithelial apoptosis but not yet known. We investigated the expression pattern of the family genes in the upper gastrointestinal epithelium and cancers. Reverse transcriptase-polymerase chain reaction revealed that, unlike GSDMA expressed in differentiated cells, GSDMB is expressed in proliferating cells and GSDMD in differentiating cells. GSDMC, meanwhile, is expressed in both differentiating and differentiated cells. Colony formation assay showed that GSDMB, closely related to GSDMA, has no cell-growth inhibition activity in gastric cancer cells, and that GSDMC and GSDMD, respectively, exhibit the activity with different strengths from that of GSDMA. Expression analyses of the four family genes in esophageal and GCs suggested that GSDMC and GSDMD as well as GSDMA are tumor suppressors and that GSDMB, which was amplified and overexpressed in some GCs, could be an oncogene. The results of the expression analysis and colony formation assay suggest that each family gene may have a distinct function in the upper gastrointestinal epithelium.