In Nonfunctional Pituitary Adenomas, Estrogen Receptors and Slug Contribute to Development of Invasiveness
In Nonfunctional Pituitary Adenomas, Estrogen Receptors and Slug Contribute to Development of Invasiveness
复制标题
在无功能性垂体腺瘤中，雌激素受体和鼻塞有助于侵袭性的发展
DOI：
10.1210/jc.2010-3040
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发表时间：
2011-08-01
影响因子：
5.8
通讯作者：
Fan, Xiaotang
中科院分区：
文献类型：
--
作者：
Zhou, Wei;Song, Yechun;Fan, Xiaotang
内容：临床研究表明，雌激素受体（ER）-α和ER β的作用失衡与上皮来源的肿瘤侵袭有关。这两种ER在垂体腺瘤（PA）中均被检测到。我们的前期研究和其他报道表明，ER α和ER β之间的失衡有助于PA的发病机制和生物学行为，包括侵袭。目的：检测41例非功能性PA（non-functional PA，NFPA）组织中ER、Slug和E-cadherin的表达，探讨ER与NFPA侵袭性的关系。方法：采用免疫组化、RT-PCR、Western blot等方法，检测侵袭性NFPA中ER α的表达，并与E-cadherin、Slug的表达进行相关性分析。侵袭性NFPA的ER β染色较非侵袭性NFPA明显减弱（P < 0.01）。侵袭性NFPA中E-cadherin mRNA和蛋白表达均低于非侵袭性NFPA。E-cadherin的抑制因子Slug在侵袭性NFPA中的表达明显高于非侵袭性NFPA（P < 0.01）。在NFPA中，ER与Slug和E-cadherin均呈显著相关，其中Slug与ER α呈正相关，与ER β呈负相关，E-cadherin与ER β呈正相关，与ER α呈负相关。结论：ER α和ER β可能通过相反的方向调节Slug-E-cadherin通路，影响NFPA的侵袭性。（临床内分泌代谢杂志96：E1237-E1245，2011）
Context: Clinical studies suggest that an imbalance in the actions of estrogen receptor (ER)-alpha and ER beta is associated with invasion of tumors of epithelial origin. Both ER have been detected in the pituitary adenomas (PA). Our previous study together with other reports suggests that an imbalance between ER alpha and ER beta contributes to the pathogenesis and biological behavior of PA including invasion. However, the roles of the two ER in invasiveness of PA have not been clarified.Objective: The expression of ER, Slug, and E-cadherin in 41 cases of nonfunctional PA (NFPA) were determined to evaluate whether ER were related to the invasiveness of NFPA. Furthermore, we aimed by analysis of the correlation between ER and E-cadherin or Slug to understand molecular mechanisms related to invasiveness.Methods: Immunohistochemistry, RT-PCR, and Western blot were performed.Results: Nuclear ER alpha staining was significantly stronger in invasive NFPA than noninvasive ones (P < 0.01). In contrast, nuclear ER beta staining was significantly weaker in invasive NFPA than in noninvasive ones (P < 0.01). Both E-cadherin mRNA and protein were decreased in invasive NFPA compared with noninvasive ones. Moreover, Slug, a repressor of E-cadherin, was significantly increased in invasive over noninvasive NFPA (P < 0.01). There were significant correlations between ER and Slug or E-cadherin in NFPA, in which Slug was positively correlated with ER alpha and inversely correlated with ER beta, whereas E-cadherin was positively correlated with ER beta and inversely correlated with ER alpha.Conclusions: ER alpha and ER beta may act in opposite directions to regulate the Slug-E-cadherin pathway and to affect invasiveness of NFPA. (J Clin Endocrinol Metab 96: E1237-E1245, 2011)