Estrogen-related receptor alpha induces the expression of vascular endothelial growth factor in breast cancer cells.
Estrogen-related receptor alpha induces the expression of vascular endothelial growth factor in breast cancer cells.
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DOI：
10.1016/j.jsbmb.2009.02.010
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发表时间：
2009-03
影响因子：
4.1
通讯作者：
McDonnell, Donald P.
中科院分区：
文献类型：
--
作者：
Stein, Rebecca A.;Gaillard, Stephanie;McDonnell, Donald P.
雌激素相关受体α(ERRα)是核受体转录因子家族中的孤儿成员。ERRα除了具有代谢调节功能外，还与多种恶性肿瘤的生长和发展有关。在乳腺癌的背景下，Errα不仅是一个假定的负面预后因素，而且我们最近发现，在这种疾病的异种移植模型中，它的表达下调会抑制肿瘤的生长。然而，ERRα功能在乳腺癌中发挥作用的具体方面仍不清楚。以辅活化子pGC-1α作为调节ERR-α活性的蛋白质配体，分析该受体对ER-α阳性细胞系基因表达的影响。这一分析导致了大量潜在的ERRα靶基因的鉴定，其中许多基因随后在其他乳腺癌细胞系中得到了验证。重要的是，我们在这项研究中证明，在几个不同的乳腺癌细胞系中，ERRα的激活导致了VEGFmRNA表达的显著增加，这种活性转化为VEGF蛋白分泌的增加。血管内皮生长因子的诱导是错误α与血管内皮生长因子启动子中特定的错误反应元件相互作用的结果。这些发现表明，ERRα依赖的血管内皮生长因子的诱导可能有助于在表达ERRα的肿瘤中观察到总体的阴性表型，并为其作为癌症治疗靶点的使用提供了验证。
Estrogen-related receptor alpha (ERRα) is an orphan member of the nuclear receptor family of transcription factors. In addition to its function as a metabolic regulator, ERRα has been implicated in the growth and progression of several malignancies. In the setting of breast cancer, not only is ERRα a putative negative prognostic factor, but we have recently found that knockdown of its expression retards tumor growth in a xenograft model of this disease. The specific aspects of ERRα function that are responsible for its actions in breast cancer, however, remain unclear. Using the coactivator PGC-1α as a protein ligand to regulate ERRα activity, we analyzed the effects of this receptor on gene expression in the ERα-positive MCF-7 cell line. This analysis led to the identification of a large number of potential ERRα target genes, many of which were subsequently validated in other breast cancer cell lines. Importantly, we demonstrate in this study that activation of ERRα in several different breast cancer cell lines leads to a significant increase in VEGF mRNA expression, an activity that translates into an increase in VEGF protein secretion. The induction of VEGF results from the interaction of ERRα with specific ERR-responsive elements within the VEGF promoter. These findings suggest that ERRα-dependent induction of VEGF may contribute to the overall negative phenotype observed in tumors in which ERRα is expressed and provide validation for its use as a therapeutic target in cancer.
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影响因子：
6.4
作者：
Dabrosin, C;Margetts, PJ;Gauldie, J
通讯作者：
Gauldie, J
DOI：
10.1073/pnas.2235590100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Sumi, D;Ignarro, LJ
通讯作者：
Ignarro, LJ
影响因子：
64.8
作者：
GIGUERE, V;YANG, N;EVANS, RM
通讯作者：
EVANS, RM
影响因子：
4.8
作者：
NORRIS, J;FAN, DJ;MCDONNELL, DP
通讯作者：
MCDONNELL, DP
影响因子：
3.9
作者：
Liang, Yayun;Brekken, Rolf A.;Hyder, Salman M.
通讯作者：
Hyder, Salman M.