Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in upper gastrointestinal tract but significantly suppressed in human gastric cancer cells.
Amplification of proto-oncogenes associated with their over-expression is one of the critical carcinogenic events identified in human cancer cells. In many cases of human gastric cancer, a proto-oncogene ERBB-2 is co-amplified with CAB1 genes physically linked to ERBB-2, and both genes are over-expressed. The amplified region containing ERBB-2 and CAB1 was named 17q12 amplicon from its chromosomal location. The syntenic region corresponding to the 17q12 amplicon is well conserved in mouse. In this study we isolated and characterized a novel mouse gene that locates telomeric to the mouse syntenic region. Northern blot analysis using the mouse cDNA and a cloned partial cDNA of human homolog disclosed a unique expression pattern of the genes. They are expressed predominantly in the gastrointestinal (GI) tract and in the skin at a lower level. Moreover, in the GI tract, the expression is highly restricted to the esophagus and stomach. Thus, we named the mouse gene Gasdermin (Gsdm). This is the first report of a mammalian gene whose expression is restricted to both upper GI tract and skin. Interestingly, in spite of its expression in normal stomach, no transcript was detected by Northern blot analysis in human gastric cancer cells. These data suggest that the loss of the expression of the human homolog is required for the carcinogenesis of gastric tissue and that the gene has an activity adverse to malignant transformation of cells.
Saeki
N
N
Department of Biochemistry, Faculty of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 903-0215, Japan.
Kuwahara
Y
Y
Sasaki
H
H
Satoh
H
H
Shiroishi
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics*; D002876:Chromosomes, Bacterial / Q000235:genetics; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D004064:Digestive System / Q000378:metabolism*; D005260:Female; D051382:GRB7 Adaptor Protein; D005784:Gene Amplification; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D000090063:Proto-Oncogene Mas; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D000094524:Gasdermins
D004247:DNA; D018076:DNA, Complementary; D051382:GRB7 Adaptor Protein; D009363:Neoplasm Proteins; D011506:Proteins; D000090063:Proto-Oncogene Mas; D012313:RNA; D011993:Recombinant Fusion Proteins; C495955:GRB7 protein, human; C485887:GSDMA protein, human; D000094524:Gasdermins; C495956:Grb7 protein, mouse; C413482:Gsdma protein, mouse; C000715470:MAS1 protein, human