title: Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.
abstract: 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.
authors.affiliation: Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Saeki
authors.forename: Takebumi
authors.initials: T
authors.lastname: Usui
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Dal Ho
authors.initials: DH
authors.lastname: Kim
authors.forename: Megumi
authors.initials: M
authors.lastname: Sato
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mabuchi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D028044:Phosphate-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D000094524:Gasdermins
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D028044:Phosphate-Binding Proteins; C485887:GSDMA protein, human; D000094524:Gasdermins; C527978:GSDMB protein, human; C425469:GSDMC protein, human; C498366:GSDMD protein, human