Expression of differentiation-associated gene icb-1 is estrogen-responsive in ovarian and breast cancer cell lines
Expression of differentiation-associated gene icb-1 is estrogen-responsive in ovarian and breast cancer cell lines
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DOI：
10.1016/j.jsbmb.2007.12.007
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发表时间：
2008-03-01
影响因子：
4.1
通讯作者：
Treeck, Oliver
中科院分区：
文献类型：
--
作者：
Bollmann, Julia;Ortmann, Olaf;Treeck, Oliver
icb-1（Clorf 38）是一个人类基因，最初由我们的小组描述为在由不同刺激触发的子宫内膜腺癌和白血病细胞的体外分化过程中上调。我们现在报告的icb-1基因的启动子中存在一个假定的不完善的雌激素反应元件（ERE）。已知雌激素可以调节依赖雌二醇的组织的细胞分化过程，我们研究了乳腺癌和卵巢癌细胞中icb-1的表达是否会受到17-beta雌二醇的调节。通过真实的时间PCR检测，用17-β雌二醇处理至少24小时导致ER α阳性MCF-7乳腺癌和OVCAR-3卵巢癌细胞中icb-1转录水平显著增加，但在ER α阴性SK-BR-3和SK-OV-3细胞中没有。在MCF-7和OVCAR-3卵巢癌细胞中，用特异性ER α-激动剂PPT处理后也观察到icb-1转录水平的上调，并通过与纯抗雌激素ICI 182，780共处理而抑制。放线菌酮治疗完全抑制雌激素的作用，表明icb-1基因表达的激活是没有雌激素依赖性的早期反应，但需要蛋白质合成的继发事件。本研究的结果表明，分化相关基因icb-1的转录水平在乳腺癌和卵巢癌细胞中以ER α依赖的方式对雌激素敏感。icb-1是否是雌激素触发的细胞分化过程中的一个介导因子，还有待于进一步的研究。(C)2007爱思唯尔有限公司保留所有权利。
icb-1 (Clorf38) is a human gene initially described by our group to be upregulated during in vitro differentiation processes of endometrial adenocarcinoma and leukemia cells triggered by different stimuli. We now report presence of a putative imperfect estrogen response element (ERE) in the promoter of icb-1 gene. Given that estrogens are known to regulate cellular differentiation processes of hormone-dependent tissues, we studied whether expression of icb-1 would be regulated by 17-beta (beta) estradiol in breast and ovarian cancer cells. As examined by means of real time PCR, treatment with 17-beta estradiol for at least 24 h resulted in a significant increase of icb-1 transcript levels in ER alpha-positive MCF-7 breast cancer and OVCAR-3 ovarian cancer cells, but not in ER alpha-negative SK-BR-3 and SK-OV-3 cells. Upregulation of icb-1 transcript levels was also observed after treatment with specific ER alpha-agonist PPT and was inhibited by co-treatment with pure antiestrogen ICI 182,780 in MCF-7 and OVCAR-3 ovarian cancer cells. Treatment with cycloheximide totally inhibited estrogen effects suggesting that activation of icb-1 gene expression is no ERE-dependent early response but a secondary event requiring protein synthesis. The results of this study demonstrate that transcript levels of differentiation-associated gene icb-1 are estrogen-responsive in breast and ovarian cancer cells in an ER alpha-dependent manner. Whether icb-1 is a mediator of estrogen-triggered cellular differentiation processes has to be determined in further studies. (C) 2007 Elsevier Ltd. All rights reserved.