Cloning and characterization of two promoters for the human calcium-sensing receptor (CaSR) and changes of CaSR expression in parathyroid adenomas

被引:72
作者
Chikatsu, N
Fukumoto, S
Takeuchi, Y
Suzawa, M
Obara, T
Matsumoto, T
Fujita, T
机构
[1] Univ Tokyo, Branch Hosp, Dept Lab Med, Bunkyo Ku, Tokyo 1128688, Japan
[2] Univ Tokyo, Branch Hosp, Dept Internal Med, Bunkyo Ku, Tokyo 1128688, Japan
[3] Tokyo Womens Med Univ, Dept Endocrine Surg, Tokyo 1628666, Japan
[4] Univ Tokushima, Dept Internal Med 1, Tokushima 7708503, Japan
关键词
D O I
10.1074/jbc.275.11.7553
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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.
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页码:7553 / 7557
页数:5
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