Cloning and characterization of two promoters for the human calcium-sensing receptor (CaSR) and changes of CaSR expression in parathyroid adenomas
Cloning and characterization of two promoters for the human calcium-sensing receptor (CaSR) and changes of CaSR expression in parathyroid adenomas
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DOI：
10.1074/jbc.275.11.7553
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发表时间：
2000-03-17
影响因子：
4.8
通讯作者：
Fujita, T
中科院分区：
文献类型：
--
作者：
Chikatsu, N;Fukumoto, S;Fujita, T
组织学分析表明，甲状旁腺腺瘤中甲状旁腺钙敏感受体（CaSR）的表达降低。由于CaSR表达降低可能导致甲状旁腺激素分泌抑制不足，因此阐明CaSR表达的调控机制对于了解甲状旁腺腺瘤的发病机制是必不可少的。然而，人CaSR启动子区的结构和多种CaSR mRNA的产生机制尚不清楚。我们通过筛选基因组文库克隆了人CaSR的启动子区。人CaSR基因具有两个启动子和两个5 '端非翻译外显子（外显子1A和1B），这些外显子的交替使用导致产生多个CaSR mRNA。上游启动子具有TATA和CAAT盒，下游启动子富含GC。北方杂交结果显示，甲状旁腺腺瘤中外显子1A的表达水平明显低于正常腺体。外显子1B在腺瘤和正常腺体中的表达无明显差异。因此，在甲状旁腺腺瘤中观察到由上游启动子驱动的转录物的特异性减少，需要进一步分析调节上游启动子活性的因素以阐明甲状旁腺腺瘤的发病机制。
Histological analyses showed that expression of the parathyroid calcium-sensing receptor (CaSR) is decreased in parathyroid adenomas, Because reduced expression of CaSR may result in insufficient suppression of parathyroid hormone secretion, the elucidation of regulatory mechanisms of CaSR expression is indispensable for understanding the pathogenesis of parapthyroid adenomas, Two cDNA clones for human CaSR with different 5'-untranslated regions have been isolated. However, the structure of the promoter region of human CaSR and the mechanisms of production of multiple CaSR mRNAs are unknown. We have cloned promoter regions of human CaSR by screening a genomic library. The human CaSR gene has two promoters and two 5'-untranslated exons (exons 1A and 1B), and alternative usage of these exons leads to production of multiple CaSR mRNAs, The upstream promoter has TATA and CAAT boxes, and the downstream promoter is GC-rich. Northern blot analysis showed that expression levels of exon 1A in parathyroid adenomas are significantly less than those in normal glands. However, expression of exon 1B was not different between adenomas and normal glands. Thus, specific reduction of the transcript driven by the upstream promoter was observed in parathyroid adenomas, Further analyses of factors that modulate the activity of the upstream promoter are necessary to clarify the pathogenesis of parathyroid adenomas.