孤儿受体COUP-TFI与共抑制因子在肾上腺肿瘤中的差异表达。

Differential expression of an orphan receptor COUP-TFI and corepressors in adrenal tumors.

作者信息

Shibata H, Ando T, Suzuki T, Kurihara I, Hayashi K, Hayashi M, Saito I, Kawabe H, Tsujioka M, Mural M, Saruta T

机构信息

Health Center and Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

出版信息

Endocr Res. 1998 Aug-Nov;24(3-4):881-5. doi: 10.3109/07435809809032703.

DOI:10.3109/07435809809032703

PMID:9888593

Abstract

Recently, it has been shown that CYP17 gene transcription is activated by SF-1 (Steroidogenic Factor-1) binding to a cyclic AMP-responsive sequence within the promoter region of the gene, whereas it is inhibited by COUP-TF (Chicken Ovalbumin Upstream Promoter-Transcription Factor) binding to the sequence. We have shown that transcriptional repression by COUP-TFI is mediated by corepressors, N-CoR (nuclear receptor corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone-receptor). Therefore, we compared the expression of COUP-TFI, N-CoR and SMRT in non-hyperfunctioning adrenocortical adenomas and normal adrenal glands. We found significantly higher expression of COUP-TFI mRNA in non-hyperfunctioning adenomas (n=5, 227+/-18%) than in normal adrenals (n=5, 96+/-4%). Interestingly, the pattern of N-CoR and SMRT expression was different compared with COUP-TFI expression. These data suggest that COUP-TFI, N-CoR, and SMRT may play a differential role in steroid biosynthesis of non-hyperfunctioning adenomas.

摘要

最近的研究表明，CYP17基因转录通过类固醇生成因子1（SF-1）与该基因启动子区域内的环磷酸腺苷反应序列结合而被激活，而通过鸡卵清蛋白上游启动子转录因子（COUP-TF）与该序列结合则受到抑制。我们已经表明，COUP-TFI介导的转录抑制是由共抑制因子核受体共抑制因子（N-CoR）和视黄酸及甲状腺激素受体沉默介质（SMRT）介导的。因此，我们比较了COUP-TFI、N-CoR和SMRT在非高功能性肾上腺皮质腺瘤和正常肾上腺中的表达。我们发现，非高功能性腺瘤（n = 5，227±18%）中COUP-TFI mRNA的表达明显高于正常肾上腺（n = 5，96±4%）。有趣的是，与COUP-TFI表达相比，N-CoR和SMRT的表达模式有所不同。这些数据表明，COUP-TFI、N-CoR和SMRT可能在非高功能性腺瘤的类固醇生物合成中发挥不同的作用。