Expression of estrogen receptors-α and -β in bladder cancer cell lines and human bladder tumor tissue
Expression of estrogen receptors-α and -β in bladder cancer cell lines and human bladder tumor tissue
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DOI：
10.1002/cncr.21945
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发表时间：
2006-06-15
期刊：
影响因子：
6.2
通讯作者：
Lerner, Seth P.
中科院分区：
文献类型：
--
作者：
Shen, Steven S.;Smith, Carolyn L.;Lerner, Seth P.
背景雌激素受体（ER）是已知的介导重要的生理反应，以及响应于雌二醇刺激的一些肿瘤的生长。在先前的研究中，选择性ER调节剂雷洛昔芬显示在ER β阳性膀胱癌细胞系中诱导细胞凋亡。然而，ER β在人膀胱癌中的表达尚未得到彻底的研究。采用组织芯片和免疫组化技术检测224例膀胱肿瘤组织中ER α和ER β的表达。使用定量逆转录聚合酶链反应（RT-PCR）和Western印迹分析，在几种膀胱癌细胞系中确定ER α和ER β蛋白和mRNA的表达水平。雌二醇和抗雌激素治疗对RT 4膀胱癌细胞生长的影响通过细胞增殖测定来确定。分析显示，只有2例人膀胱癌弱表达ER α。相比之下，在141个肿瘤（63%）中检测到ER β的表达。ER β在58%的WHO 1级和2级肿瘤中表达，而70%的3级肿瘤表达（P= 0.085）。重要的是，尽管Ta和T1肿瘤中只有53%和55%显示ER β表达，但T2、T3和T4肿瘤中分别有80%、81%和75%显示ERA表达。ER β在Ta/T1和T2/T3/T4肿瘤中的表达差异有显著性（P
BACKGROUND. Estrogen receptors (ERs) are known to mediate important physiologic responses as well as the growth of some tumors in response to estradiol stimulation. In a previous study the selective ER modulator raloxifene was shown to induce apoptosis in an ER beta-positive bladder cancer cell line. However, the expression of ER beta in human bladder cancer has not been thoroughly investigated.METHODS. ER alpha and ER beta expression in 224 bladder tumor samples was evaluated using tissue microarray and immunohistochemistry. Levels of ER alpha and ER beta protein and mRNA expression were determined in several bladder cancer cell lines using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. The effect of estradiol and antiestrogen treatments on RT4 bladder cancer cell growth was determined by cell proliferation assays.RESULTS. Analyses revealed that only 2 human bladder cancers weakly expressed ERa. In contrast, the expression of ER beta was detected in 141 tumors (63%). ER beta was expressed in 58% of WHO Grade 1 and 2 tumors, whereas 70% of Grade 3 tumors demonstrated expression (P=.085). Importantly, although only 53% and 55% of Ta and T1 tumors demonstrated ER beta expression, 80% of T2,81% of T3, and 75% of T4 tumors showed ERA expression. The differences in ER beta expression between Ta/T1 and T2/T3/T4 tumors were found to be highly significant (P