FoxA1 Specifies Unique Androgen and Glucocorticoid Receptor Binding Events in Prostate Cancer Cells
FoxA1 Specifies Unique Androgen and Glucocorticoid Receptor Binding Events in Prostate Cancer Cells
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DOI：
10.1158/0008-5472.can-12-2350
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发表时间：
2013-03-01
期刊：
影响因子：
11.2
通讯作者：
Janne, Olli A.
中科院分区：
文献类型：
--
作者：
Sahu, Biswajyoti;Laakso, Marko;Janne, Olli A.
叉头蛋白FoxA1具有先锋因子以外的功能，因为它的缺失会导致雄激素受体（AR）和糖皮质激素受体（GR）基质中的显著重新分布。在这项研究中，我们发现FoxA1具有一种新的功能，它以一种独特的方式定义AR和GR结合事件的细胞类型特异性，即LNCaP-1F5细胞中的AR和VCaP细胞中的GR。我们还发现了不同的细胞类型和受体特异性的顺式元件富集在ar和gr结合位点附近。AR通路是前列腺癌生物学的核心，但GR的作用尚不清楚。我们发现AR和GR的基质和转录程序有明显的重叠，并且GR调节了大量被认为是AR通路特异性的基因。这就提出了GR在去势抵抗性前列腺癌患者雄激素缺乏条件下维持AR通路中的作用的问题。然而，在雄激素存在的情况下，配体占据的GR作为部分抗雄激素并减弱ar依赖的转录程序。癌症Res;73 (5);1570 - 80。(c) 2012年aacr。
The forkhead protein FoxA1 has functions other than a pioneer factor, in that its depletion brings about a significant redistribution in the androgen receptor (AR) and glucocorticoid receptor (GR) cistromes. In this study, we found a novel function for FoxA1 in defining the cell-type specificity of AR- and GR-binding events in a distinct fashion, namely, for AR in LNCaP-1F5 cells and for GR in VCaP cells. We also found different, cell-type and receptor-specific compilations of cis-elements enriched adjacent to the AR-and GR-binding sites. The AR pathway is central in prostate cancer biology, but the role of GR is poorly known. We find that AR and GR cistromes and transcription programs exhibit significant overlap, and GR regulates a large number of genes considered to be AR pathway-specific. This raises questions about the role of GR in maintaining the AR pathway under androgen-deprived conditions in castration-resistant prostate cancer patients. However, in the presence of androgen, ligand-occupied GR acts as a partial antiandrogen and attenuates the AR-dependent transcription program. Cancer Res; 73(5); 1570-80. (C) 2012 AACR.