Differential expression of estrogen receptor alpha (ERalpha) protein in MCF-7 breast cancer cells chronically exposed to TCDD.
Differential expression of estrogen receptor alpha (ERalpha) protein in MCF-7 breast cancer cells chronically exposed to TCDD.
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长期暴露于 TCDD 的 MCF-7 乳腺癌细胞中雌激素受体 α (ERα) 蛋白的差异表达。
DOI：
10.1002/jcb.21438
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发表时间：
2008
影响因子：
4
通讯作者：
Gierthy,JohnF
中科院分区：
文献类型：
--
作者：
Marquez-Bravo,LydiaG;Gierthy,JohnF
雌激素在乳腺癌肿瘤的发生和进化中发挥着关键作用。雌激素受体α（ERα）介导雌激素的许多生物活性，其表达与低侵袭性和良好预后相关。最近的流行病学报告表明，长期接触 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 与接触该物质的女性乳腺癌发病率增加有关。 TCDD 干扰一些 ERα 依赖性基因的表达，并在体外抑制雌二醇 (E2) 依赖性乳腺癌细胞的生长。然而，MCF-7 人类乳腺癌细胞的 E2 依赖性异种移植在暴露于 TCDD 两周后恢复了生长。细胞生长恢复的机制尚不完全清楚。在这项研究中，我们表明短期暴露于 1 nM TCDD 会导致 ERα 蛋白表达受到抑制，而长期暴露超过 1 年（LTDX 细胞）会导致受体部分重新表达。免疫细胞化学研究表明，LTDX 细胞中的 ERα 在某些细胞中重新表达。蛋白质免疫印迹分析表明，五分之四的 LTDX 克隆的 ERα 表达水平与未暴露的 MCF-7 细胞相当。取消 TCDD 治疗 16 天后，ERα 阴性克隆细胞中 ERα 的表达得以恢复。这些结果表明，长期暴露于 TCDD 的 MCF-7 细胞至少含有两个细胞亚群，它们可能对 TCDD 的 ERα 介导作用产生不同的反应。 J.细胞。生物化学。 103: 636–647, 2008。© 2007 Wiley-Liss, Inc.
Estrogens play a key role in the development and evolution of breast cancer tumors. Estrogen receptor alpha (ERα) mediates many of the biological activities of estrogens, and its expression is associated with low invasiveness and good prognosis. Recent epidemiological reports suggest that long‐term exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is implicated in the increased incidence of breast cancer in exposed women. TCDD interferes with the expression of some ERα‐dependent genes and inhibits estradiol (E2)‐ dependent growth of breast cancer cells in vitro. However, E2‐dependent xenographs of MCF‐7 human breast cancer cells resumed growth after a 2‐week exposure to TCDD. The mechanisms involved in the resumption of cell growth are not completely understood. In this study, we show that short term‐exposure (16 days) to 1 nM TCDD results in the suppression of ERα protein expression, while chronic exposure for more than 1 year (LTDX cells) results in the partial re‐expression of the receptor. Immunocytochemistry studies showed that re‐expression of ERα in LTDX cells occurred in some of the cells. Analysis by Western immunoblots indicated that four out of five LTDX clones expressed ERα at levels comparable to those in unexposed MCF‐7 cells. Removal of TCDD treatment for 16 days restored the expression of ERα in the ERα‐negative clonal cells. These results suggest that MCF‐7 cells chronically exposed to TCDD contain at least two cell subpopulations that may respond differently to the ERα‐mediated effects of TCDD. J. Cell. Biochem. 103: 636–647, 2008. © 2007 Wiley‐Liss, Inc.