Differential expression and localisation of gasdermin-like (GSDML), a novel member of the cancer-associated GSDMDC protein family, in neoplastic and non-neoplastic gastric, hepatic, and colon tissues
Differential expression and localisation of gasdermin-like (GSDML), a novel member of the cancer-associated GSDMDC protein family, in neoplastic and non-neoplastic gastric, hepatic, and colon tissues
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DOI：
10.1080/00313020701716250
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发表时间：
2008-01-01
期刊：
影响因子：
4.5
通讯作者：
Roecken, Christoph
中科院分区：
文献类型：
--
作者：
Carl-Mcgrath, Stacy;Schneider-Stock, Regine;Roecken, Christoph
目的：Gasdermin样蛋白（GSDML）是肿瘤相关Gasdermin结构域蛋白（GSDMDC）家族的新成员。GSDMDC家族与肿瘤的发生和发展有关，这是第一次研究分析GSDML.Methods的表达和细胞内定位：GSDML基因的转录进行了分析，采用定量实时RT-PCR。抗GSDML的抗肽抗体在兔中被开发，并且体外转录-翻译反应被用于验证特异性。结果：GSDML基因在人胃、肝、结肠癌细胞系、癌组织及癌旁组织中均有转录，在人胃癌、胃癌、结直肠癌及癌旁组织中均有表达。GSDML蛋白定位于肿瘤和非病变组织的细胞质。GSDML蛋白剪接变体的分子量范围为35至50 kDa，并且表达谱在肿瘤和非肿瘤之间变化。GSDML在胃主细胞和结肠表面粘液细胞的顶端区域以及神经内分泌细胞的基底区域表现出独特的囊泡染色模式。结论：GSDML可能是参与分泌途径的分泌或代谢产物，GSDML剪接变异体转录和翻译调控的改变可能在胃肠道和肝癌的发生和/或发展中可见。
Aim: Gasdermin-like (GSDML) is a novel member of the cancer associated gasdermin-domain containing (GSDMDC) protein family. The GSDMDC family has been linked to cancer development and progression, and this is the first study analysing the expression and intracellular localisation of GSDML.Methods: GSDML gene transcription was analysed using quantitative real-time RT-PCR. Anti-peptide antibodies against GSDML were developed in rabbits, and an invitro transcription-translation reaction was used to verify specificity. The Protein-G affinity purified antibodies were used in immunohistochemistry and immunoblotting on hepatocellular, gastric, and colorectal carcinomas and non-lesional tissues.Results: The GSDML gene was transcribed in human gastric, liver and colon cell lines, carcinomas and non-lesional tissues. The GSDML protein was localised to the cytoplasm of cells in both tumour and non-lesional tissues. The GSDML protein splicing variants range in molecular weight from 35 to 50kDa, and the expression profile varies between tumour and non-tumour. A distinctive vesicular staining pattern was exhibited by GSDML in the apical region of gastric chief cells and colonic surface mucous cells, and the basal region of neuroendocrine cells.Conclusion: GSDML may be a secretory or metabolic product involved in a secretory pathway, and changes in the regulation of GSDML splicing variant transcription and translation may be seen in the development and/or progression of gastrointestinal and hepatic cancers.