Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues
Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues
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DOI：
10.1210/jc.2004-1421
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发表时间：
2005-03-01
影响因子：
5.8
通讯作者：
Chan, FL
中科院分区：
文献类型：
--
作者：
Cheung, CP;Yu, S;Chan, FL
雌激素受体相关受体（ERR; α、β、γ）是孤儿核受体，并且具有组成性活性而不与雌激素结合。与雌激素受体（ER）一样，ERR与雌激素受体元件和雌激素受体元件相关重复序列结合。越来越多的证据表明，ERRs可以通过竞争DNA位点和共激活因子与不同细胞类型中的ER发生交叉作用。我们推测ERRs可能通过共享相似的ER介导的通路或独立作用在正常和肿瘤前列腺细胞中发挥调节作用。在这项研究中，我们研究了正常人前列腺上皮细胞，已建立的细胞系，癌症异种移植物和前列腺组织中的三个ERR成员的mRNA和蛋白质表达模式。此外，还检测了ERRs瞬时转染对前列腺细胞增殖和ER表达的影响。RT-PCR显示ERR α和ERR γ转录本在大多数细胞系和异种移植物中检测到，而ERR β在正常上皮细胞和少数永生化细胞系中检测到，但在大多数癌细胞系中未检测到。在临床前列腺标本中证实了类似的结果。Western印迹和免疫组化证实了类似的表达模式，ERR蛋白在上皮细胞中被检测为核蛋白，而它们的表达在肿瘤性前列腺细胞中变得减少或未检测到。瞬时转染证实，ERRs在前列腺细胞中表达为核蛋白，并且在没有雌二醇的情况下具有转录活性。转染结果显示ERRs的过表达抑制PC-3细胞的增殖和ER α的转录。我们的研究表明，ERRs与ER在前列腺细胞中共表达，可以通过干扰前列腺细胞中ER α的转录来调节细胞生长和ER介导的通路。
Estrogen receptor-related receptors (ERRs; alpha, beta, gamma) are orphan nuclear receptors and constitutively active without binding to estrogen. Like estrogen receptors ( ERs), ERRs bind to estrogen receptor elements and estrogen receptor element-related repeats. Growing evidence suggests that ERRs can cross-talk with ERs in different cell types via competition for DNA sites and coactivators. We hypothesize that ERRs might play regulatory roles in normal and neoplastic prostatic cells by sharing similar ER-mediated pathways or acting independently. In this study, we investigated mRNA and protein expression patterns of three ERR members in normal human prostate epithelial cells, established cell lines, cancer xenografts, and prostatic tissues. Additionally, effects of transient transfection of ERRs on prostatic cell proliferation and ER expression were also examined. RT-PCR showed that ERR alpha and ERR gamma transcripts were detected in most cell lines and xenografts, whereas ERR beta was detected in normal epithelial cells and few immortalized cell lines but not in most cancer lines. Similar results were demonstrated in clinical prostatic specimens. Western blottings and immunohistochemistry confirmed similar expression patterns that ERR proteins were detected as nuclear proteins in epithelial cells, whereas their expressions became reduced or undetected in neoplastic prostatic cells. Transient transfection confirmed that ERRs were expressed in prostatic cells as nuclear proteins and transcriptionally active in the absence of estradiol. Transfection results showed that overexpression of ERRs inhibited cell proliferation and repressed ER alpha transcription in PC-3 cells. Our study shows that ERRs, which are coexpressed with ERs in prostatic cells, could regulate cell growth and modulate ER-mediated pathways via interference on ER alpha transcription in prostatic cells.