Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in upper gastrointestinal tract but significantly suppressed in human gastric cancer cells

Abstract

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.

GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-β-dependent apoptotic signalling

“…Thus, we concluded that this cDNA clone encodes human GSDM. Mouse Gsdm expression has been identified in the esophagus, stomach and skin (Saeki et al, 2000). Human GSDM mRNA, in a similar manner, was detected in the epithelium of the stomach, esophagus, mammary gland and skin (Figure 1 and data not shown).…”

“…The human cDNA clone obtained has 89% similarity in amino-acid sequence to mouse Gsdm (data not shown). A database search revealed that the human cDNA sequence is located on the human chromosome 17q21, which is syntenic to the region containing Gsdm on mouse chromosome 11 and genomic Southern blot analysis demonstrated that only one Gsdm homolog is present in the human genome (Saeki et al, 2000). Thus, we concluded that this cDNA clone encodes human GSDM.…”

“…TGF-b/LMO1/GSDM pathway in gastric pit cells N Saeki et al et al, 2000). The mature pit cells are known to containa significant amount of mucus in their cytoplasm.…”

“…GASDERMIN (GSDM) is a human homolog of mouse gene Gasdermin (Gsdm), which was isolated by positional cloning as a candidate of the gene responsible for two mouse mutants with epidermal hyperplasia: recombination-induced mutation 3 (Rim3) and Rex denuded (Re den ) (Sato et al, 1998;Saeki et al, 2000). Gasdermin 3 (Gsdm3), one of the mouse homolog of GSDM/Gsdm, was reported as the responsible gene for Rim3 and other mutant mice with skin phenotype, and is considered to have some role in the epidermal differentiation (Runkel et al, 2004;Lunny et al, 2005).…”

“…Gasdermin 3 (Gsdm3), one of the mouse homolog of GSDM/Gsdm, was reported as the responsible gene for Rim3 and other mutant mice with skin phenotype, and is considered to have some role in the epidermal differentiation (Runkel et al, 2004;Lunny et al, 2005). Human GSDM is preferentially expressed in the gastric epithelium, but frequently silenced in gastric cancer cell lines (Saeki et al, 2000). These findings in humans and mice suggest the possibility that GSDM/Gsdm contribute to the regulation of normal epithelial cell proliferation and/or differentiation.…”