Involvement of estrogen receptor β in ovarian carcinogenesis (Retracted article. See vol 65, pg 5480, 2005)
Involvement of estrogen receptor β in ovarian carcinogenesis (Retracted article. See vol 65, pg 5480, 2005)
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DOI：
10.1158/0008-5472.can-04-0552
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发表时间：
2004-08-15
期刊：
影响因子：
11.2
通讯作者：
Lazennec, G
中科院分区：
文献类型：
--
作者：
Bardin, A;Hoffmann, P;Lazennec, G
敲除和表达研究表明，雌激素受体β（ER β）在卵巢功能和病理中起着重要作用。此外，卵巢癌的特征在于高发病率和对抗雌激素的低反应性。在这里，我们证明，使用定量PCR测量ER α和ER β水平在58例卵巢癌患者，ER β表达减少囊肿和卵巢癌相比，正常卵巢，这种减少是由于在ER β表达的选择性损失在癌症的进展。为了解决ER β可能参与卵巢癌的问题，我们使用腺病毒递送恢复了两种人卵巢癌细胞系PEO 14（ER α阴性）和BG 1（ER α阳性）中ER α和ER β的表达。ER α能诱导孕激素受体和fibulin-IC的表达，而ER β则不能。此外，ER α和ER β对细胞周期蛋白D1基因的调控作用相反，因为ER β下调细胞周期蛋白D1基因的表达，而ER α增加细胞周期蛋白D1的水平。有趣的是，ER β表达强烈抑制PEO 14和BG 1细胞增殖和细胞运动的配体非依赖性的方式，而ER α没有显着的效果。如Annexin V染色所示，ER β诱导的凋亡也有助于卵巢癌细胞增殖的降低。这项研究表明，ER β是一个重要的调节增殖和运动的卵巢癌，并提供了第一个证据ER β的促凋亡作用。因此，ER β表达的缺失可能是导致卵巢癌发展的重要事件。
Knockout and expression studies suggest that estrogen receptor beta (ERbeta) plays a prominent role in ovarian function and pathology. Moreover, ovarian cancers are characterized by high morbidity and low responsiveness to anti-estrogens. Here we demonstrate, using quantitative PCR to measure ERalpha and ERbeta levels in 58 ovarian cancer patients, that ERbeta expression decreased in cysts and ovarian carcinomas as compared with normal ovaries and that this decrease is attributable only to a selective loss in ERbeta expression during cancer progression. To address the question of a possible involvement of ERbeta in ovarian cancers, we restored ERalpha and ERbeta expression in two human ovarian cancer cell lines PEO14 (ERalpha-negative) and BG1 (ERalpha-positive) using adenoviral delivery. ERalpha, but not ERbeta, could induce progesterone receptor and fibulin-IC. Moreover, ERalpha and ERbeta had opposite actions on cyclin D1 gene regulation, because ERbeta down-regulated cyclin D1 gene expression, whereas ERalpha increased cyclin D1 levels. Interestingly, ERbeta expression strongly inhibited PEO14 and BG1 cell proliferation and cell motility in a ligand-independent manner, whereas ERalpha had no marked effect. Induction of apoptosis by ERbeta also contributed to the decreased proliferation of ovarian cancer cells, as shown by Annexin V staining. This study shows that ERbeta is an important regulator of proliferation and motility of ovarian cancer and provides the first evidence for a proapoptotic role of ERbeta. The loss of ERbeta expression may thus be an important event leading to the development of ovarian cancer.