Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells.
Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells.
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DOI：
10.3892/ijo.2014.2329
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发表时间：
2014-05
影响因子：
5.2
通讯作者：
Jordan VC
中科院分区：
文献类型：
--
作者：
Sweeney EE;Fan P;Jordan VC
长期缺乏雌激素的乳腺癌细胞模型在实验室中被用来模拟临床芳香酶抑制剂耐药的乳腺癌，并作为发现新的治疗策略的工具。MCF-7:5C和MCF-7:2A亚克隆是通过雌激素受体（ER）阳性的MCF-7细胞长期雌激素剥夺而产生的，代表了抗激素抵抗性乳腺癌。mcf -7:5细胞在雌激素（雌二醇，E2）治疗7天内发生雌激素诱导的凋亡；MCF-7:2A细胞也经历e2诱导的凋亡，但直到大约14天的治疗后才会出现剧烈的细胞死亡。为了发现和确定MCF-7:2A细胞在E2处理两周后存活的机制，本研究进行了系统的实验。数据表明，MCF-7:2A细胞比MCF-7:5C细胞具有更强的抗氧化防御机制，并且MCF-7:2A细胞在E2处理下死亡最终需要氧化应激。肿瘤坏死因子（TNF）家族成员的激活也是e2诱导MCF-7:2A细胞发生凋亡的必要条件；TNFα的上调与氧化应激激活同时发生。虽然未折叠蛋白反应（UPR）信号模式与MCF-7:5C细胞相似，但在MCF-7:2A细胞中并不足以导致细胞死亡。此外，增加的胰岛素样生长因子受体β (IGF-1Rβ)在MCF-7:2A细胞中具有生长和抗凋亡优势的机制。
Models of long-term estrogen-deprived breast cancer cells are utilized in the laboratory to mimic clinical aromatase inhibitor-resistant breast cancer and serve as a tool to discover new therapeutic strategies. The MCF-7:5C and MCF-7:2A subclones were generated through long-term estrogen deprivation of estrogen receptor (ER)-positive MCF-7 cells, and represent anti-hormone-resistant breast cancer. MCF-7:5C cells paradoxically undergo estrogen-induced apoptosis within seven days of estrogen (estradiol, E2) treatment; MCF-7:2A cells also experience E2-induced apoptosis but evade dramatic cell death until approximately 14 days of treatment. To discover and define the mechanisms by which MCF-7:2A cells survive two weeks of E2 treatment, systematic experiments were performed in this study. The data suggest that MCF-7:2A cells employ stronger antioxidant defense mechanisms than do MCF-7:5C cells, and that oxidative stress is ultimately required for MCF-7:2A cells to die in response to E2 treatment. Tumor necrosis factor (TNF) family member activation is also essential for E2-induced apoptosis to occur in MCF-7:2A cells; upregulation of TNFα occurs simultaneously with oxidative stress activation. Although the unfolded protein response (UPR) signaling pattern is similar to that in MCF-7:5C cells, it is not sufficient to cause cell death in MCF-7:2A cells. Additionally, increased insulin-like growth factor receptor β (IGF-1Rβ) confers a mechanism of growth and anti-apoptotic advantage in MCF-7:2A cells.
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影响因子：
10.3
作者：
Lewis, JS;Meeke, K;Jordan, VC
通讯作者：
Jordan, VC
DOI：
10.1073/pnas.1115188108
发表时间：
2011-11-22
影响因子：
11.1
作者：
Ariazi, Eric A.;Cunliffe, Heather E.;Jordan, V. Craig
通讯作者：
Jordan, V. Craig
影响因子：
1
作者：
Sweeney EE;McDaniel RE;Maximov PY;Fan P;Jordan VC
通讯作者：
Jordan VC
影响因子：
120.7
作者：
Ellis, Matthew J.;Gao, Feng;Siegel, Barry A.
通讯作者：
Siegel, Barry A.
影响因子：
120.7
作者：
Anderson, GL;Limacher, M;Wassertheil-Smoller, S
通讯作者：
Wassertheil-Smoller, S