DRM/GREMLIN (CKTSF1B1)定位于人类第15号染色体,在成人和胎儿大脑中高度表达。

L Z Topol, W S Modi, S Koochekpour, D G Blair
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引用次数: 60

摘要

我们绘制并鉴定了Drm/Gremlin (CKTFS1B1)的人类同源物,它是BMP拮抗剂家族的一员,与发育和转化相关的功能有关。通过筛选人类cDNA文库,我们分离到一个3.3 kb的cDNA,其中包含编码人类DRM蛋白的552 bp区域。通过体细胞杂交分析,CKTFS1B1定位在人类染色体15q13- > q15上,更准确地说,使用辐射杂交,定位在与SGNE1(分泌颗粒神经内分泌蛋白1)和RYR3 (ryanodyne受体3)相关的标记区域。Northern blot分析显示,在不同的人体组织中,包括脑、卵巢、肠和结肠,存在单一的drm特异性mRNA表达。在大脑中,DRM的表达与皮质下大核内囊周围的区域有关。DRM似乎主要在正常细胞和组织中表达,包括正常神经元、星形胶质细胞和成纤维细胞。有趣的是,我们在几位患者的正常细胞中检测到DRM表达,但在同一患者建立的肿瘤细胞系中却没有。这些数据表明,DRM的下调与肿瘤进展有关,并支持了人类DRM可能在神经胚胎发育和癌变过程中发挥重要作用的假设。
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DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in adult and fetal brain.

We have mapped and characterized the human homolog of Drm/Gremlin (CKTFS1B1), a member of a family of BMP antagonists that have been linked to both developmental and transformation-related functions. By screening a human cDNA library, we isolated a 3.3-kb cDNA containing the 552-bp region encoding the human DRM protein. CKTFS1B1 was localized on human chromosome 15q13--> q15 by somatic cell hybrid analysis and, more precisely, using radiation hybrids, to a region of markers linked to SGNE1, secretory granule neuroendocrine protein 1 and RYR3, the ryanodyne receptor 3. Northern blot analysis showed the presence of a single DRM-specific mRNA expressed in different human tissues, including brain, ovary, intestine and colon. In the brain, DRM expression is associated with the region localized around the internal capsule in the large subcortical nuclei. DRM appears to be predominantly expressed in normal cells and tissues, including normal neurons, astrocytes and fibroblasts. Interestingly, we detected DRM expression in normal cells obtained from several patients, but not in tumor cell lines established from the same patients. The data suggest that down-regulation of DRM is associated with tumor progression, and support the hypothesis that human DRM may play an important role during both neuroembryological development and carcinogenesis.

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