Cytoplasmic estrogen receptor β as a potential marker in human non-small cell lung carcinoma
Cytoplasmic estrogen receptor β as a potential marker in human non-small cell lung carcinoma
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DOI：
10.1517/14728222.2011.630664
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发表时间：
2012-03-01
影响因子：
5.8
通讯作者：
Sasano, Hironobu
中科院分区：
文献类型：
--
作者：
Verma, Mohit Kumar;Miki, Yasuhiro;Sasano, Hironobu
目的：雌激素已被报道促进肺癌发展的易感性增加。本研究旨在探讨胞浆雌激素受体β（c-ER β）在NSCLC中的作用。方法：采用免疫组化（IHC）法检测162例NSCLC中c-ER β的表达，并分析其与临床病理因素的关系。c-ER β表达的意义进一步研究使用在NSCLC细胞株的体外研究。结果：在ER β和芳香化酶阳性的NSCLC女性，c-ER β与更大的肿瘤直径显着相关，并往往与较差的总生存期。A549和LCAM 1细胞表达芳香化酶，以及c-ER β和核ER β（n-ER β）。U 0126（MAPK/细胞外信号调节激酶（ERK）抑制剂）在任一细胞系中比ICI 182780（ER阻断剂）更有效地消除由雌二醇通过c-ER β引起的MAPK磷酸化。然而，ICI 182780完全消除了雌二醇引起的雌激素反应元件（ERE）-荧光素酶活性。ICI 182780和U 0126的联合治疗在A549或LCAM 1细胞中比单独治疗有效得多。结论：ER β可能通过非基因组作用通过其胞浆形式的雌激素，以及通过n-ER β的基因组作用促进NSCLC的发生。雌激素在NSCLC中的这些作用可以通过ICI 182780和U 0126的联合治疗来消除。
Objectives: Estrogen has been reported to promote an increased susceptibility to lung cancer development. This study focusses on the role of cytoplasmic estrogen receptor beta (c-ER beta) in NSCLC.Methods: NSCLC (n = 162) cases were analyzed using immunohistochemistry (IHC) for c-ER beta expression and its association with clinicopathological variables. Significance of c-ER beta expression was further examined using in vitro studies in NSCLC cell lines.Results: Among ER beta and aromatase positive NSCLC females, c-ER beta was significantly associated with greater tumor diameter and tended to be associated with worse overall survival. A549 and LCAM1 cells expressed aromatase, as well as c-ER beta and nuclear ER beta (n-ER beta). U0126 (MAPK/extracellular-signal-regulated kinase (ERK) inhibitor) abrogated MAPK phosphorylation, caused by estradiol via c-ER beta, more effectively than ICI 182780 (ER blocker) in either cell line. However, ICI 182780 completely abrogated the estrogen responsive elements (ERE)-luciferase activity caused by estradiol. Combination therapy with ICI 182780 and U0126 turned out to be far more effective than either treatment alone in either A549 or LCAM1 cells.Conclusion: The results indicated that ER beta may contribute to NSCLC via non-genomic action of estrogen through its cytoplasmic form, in addition to the genomic actions via n-ER beta. These actions of estrogen in NSCLCs may be abrogated by combination therapy with ICI 182780 and U0126.