Orphan nuclear receptor DAX-1 in human endometrium and its disorders
Orphan nuclear receptor DAX-1 in human endometrium and its disorders
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DOI：
10.1111/j.1349-7006.2005.00101.x
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发表时间：
2005-10-01
期刊：
影响因子：
5.7
通讯作者：
Sasano, H
中科院分区：
文献类型：
--
作者：
Saito, S;Ito, K;Sasano, H
DAX-1（dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1）是一个新近发现的孤儿核受体家族成员。DAX-1作为类固醇激素产生的全局负调节剂发挥作用。它抑制肾上腺4结合蛋白（Ad 4 BP）/类固醇生成因子-1（SF-1）途径依赖性P450 arom在培养的人卵巢癌基质细胞中的表达，并作为雌激素受体（ER）的辅阻遏物。在本研究中，我们首先检测了DAX-1在46例正常周期性子宫内膜，36例子宫内膜增生症和103例子宫内膜癌中的定位，通过免疫组织化学方法来阐明DAX-1的可能参与及其与Ad 4 BP/SF-1（一种类固醇生成的通用转录因子）状态的相关性。然后，我们评估DAX-1 mRNA的表达，采用定量逆转录聚合酶链反应DAX-1在33例子宫内膜癌的进一步表征。我们随后将这些发现与病例的各种临床病理参数相关联。Ad 4 BP/SF-1免疫反应性在任何人的直肠中均未检测到。DAX-1的表达与子宫内膜癌的组织学分级呈负相关（P = 0.0003）。DAX-1在正常子宫内膜分泌期（P < 0.0001）和增生期（P <0.0001）的标记指数（LI）值均显著高于子宫内膜癌。DAX-1免疫反应性和芳香化酶mRNA的量之间没有显着的相关性。DAX-1与ER α（P = 0.006）和ER β LI（P < 0.001）之间均呈显著正相关。这些发现表明，DAX-1可能通过抑制雌激素作用来抑制子宫内膜癌的增殖和进展，可能是通过与癌细胞中存在的ER相互作用，而不是调节原位类固醇生成。
DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1) is a recently characterized member of the orphan nuclear receptor family. DAX-1 functions as a global negative regulator of steroid hormone production. It inhibits adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1 (SF-1) pathway-dependent P450arom expression in cultured human endometriotic stromal cells and acts as a corepressor for estrogen receptors (ER). In this study we first examined the localization of DAX-1 in 46 normal cycling endometria, 36 cases of endometrial hyperplasia and 103 cases of endometrial carcinoma by using immunohistochemistry to elucidate the possible involvement of DAX-1 and its correlation to the status of Ad4BP/SF-1, a universal transcription factor of steroidogenesis. We then evaluated DAX-1 mRNA expression, using quantitative reverse transcription-polymerase chain reaction for DAX-1 in 33 cases of endometrial carcinoma for further characterization. We subsequently correlated these findings with various clinicopathological parameters of the cases. Ad4BP/SF-1 immunoreactivity was not detected in any human endometria examined. A significant inverse correlation was detected between the status of DAX-1 immunoreactivity and histological grade (P = 0.0003) in enclometrial carcinoma. The labeling index (LI) values of DAX-1 in normal endometrium during the secretory phase (P < 0.0001) and hyperplasia (P < 0.0001) were significantly higher than that of carcinoma. No significant correlations were detected between DAX-1 immunoreactivity and amounts of aromatase mRNA. There was a statistically significant positive correlation between DAX-1 and ER alpha (P = 0.006) and ER beta LI (P < 0.001). These findings suggest that DAX-1 may inhibit the proliferation and progression of enclometrial carcinoma through inhibition of estrogenic actions, possibly by interacting with ER present in carcinoma cells, rather than regulating in situ steroiclogenesis.