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

Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in upper gastrointestinal tract bud significantly suppressed in human gastric cancer cells
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DOI:
10.1007/s003350010138
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发表时间:
2000-09-01
期刊:
影响因子:
2.5
通讯作者:
Shiroishi, T
Shiroishi, T
中科院分区:
生物学4区
文献类型:
--
作者:
Saeki, N;Kuwahara, Y;Shiroishi, T

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原癌基因的扩增及其过度表达是人类癌细胞中发现的关键致癌事件之一。在许多人胃癌病例中,原癌基因ERBB-2与物理连接到ERBB-2的CAB 1基因共扩增,并且两种基因都过表达。将扩增的ERBB-2和CAB 1区域命名为17 q12扩增子。对应于17 q12扩增子的同线区在小鼠中是很保守的。在这项研究中,我们分离和表征了一个新的小鼠基因,位于端粒的小鼠同线区。利用小鼠cDNA和克隆的人同源物的部分cDNA进行的北方印迹分析揭示了基因的独特表达模式。它们主要在胃肠道(GI)和皮肤中以较低水平表达。此外,在胃肠道中,表达高度限于食管和胃。因此,我们将小鼠基因命名为Gasdermin(Gsdm)。这是第一次报告的哺乳动物基因的表达仅限于上消化道和皮肤。有趣的是,尽管它在正常胃中表达,但通过北方印迹分析在人胃癌细胞中没有检测到转录本。这些数据表明,人同源物表达的丧失是胃组织癌变所必需的,并且该基因具有对细胞恶性转化不利的活性。
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 gents 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.