Activity and intracellular location of estrogen receptors alpha and beta in human bronchial epithelial cells.

Activity and intracellular location of estrogen receptors alpha and beta in human bronchial epithelial cells.
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DOI:
10.1016/j.mce.2009.01.021
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发表时间:
2009-06-16
影响因子:
4.1
通讯作者:
Klinge CM
Klinge CM
中科院分区:
医学2区
文献类型:
--
作者:
Ivanova MM;Mazhawidza W;Dougherty SM;Minna JD;Klinge CM

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肺部疾病和癌症中的性别差异已得到充分证实。我们曾报道,尽管雌激素受体(ER)表达相似,但来自女性的肺腺癌细胞存在雌激素转录反应,而男性的则没有。在此我们检验了一个假设,即正常人支气管上皮细胞(HBECs)呈现出与性别无关的雌激素反应。我们发现一小部分HBECs表达的ERβ约为ERα的两倍。ERα和ERβ位于细胞质、细胞核和线粒体中。与肺腺癌细胞不同的是,雌二醇(E2)在瞬时转染的HBECs中诱导了雌激素反应元件(ERE)介导的荧光素酶报告基因活性,且与供体性别无关。ERα - VP16的过表达增加了所有HBECs中ERE介导的转录活性。E2以细胞系特异性的方式增加,而4 - 羟基他莫昔芬和ICI 182,780抑制了HBEC的增殖和细胞周期蛋白D1的表达。总之,HBECs对ER配体的反应与性别无关,这表明在肺癌发生过程中可能获得了雌激素敏感性。
Gender differences in lung disease and cancer are well-established. We reported estrogenic transcriptional responses in lung adenocarcinoma cells from females but not males despite similar estrogen receptor (ER) expression. Here we tested the hypothesis that normal human bronchial epithelial cells (HBECs) show gender-independent estrogenic responses. We report that a small sample of HBECs express ~twice as much ERβ as ERα.ERα and ERβ were located in the cytoplasm, nucleus, and mitochondria. In contrast to lung adenocarcinoma cells, estradiol (E2) induced estrogen response element (ERE)-mediated luciferase reporter activity in transiently transfected HBECs regardless of donor gender. Overexpression of ERα-VP16 increased ERE-mediated transcriptional activity in all HBECs. E2 increased and 4-hydroxytamoxifen and ICI 182,780 inhibited HBEC proliferation and cyclin D1 expression in a cell line-specific manner. In conclusion, the response of HBECs to ER ligands is gender-independent suggesting that estrogenic sensitivity may be acquired during lung carcinogenesis.
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