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首页> 美国卫生研究院文献>Oncotarget >Lipid-sensors enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer
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Lipid-sensors enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer

机译：脂质传感器神秘孤儿和孤儿核受体作为乳腺癌的治疗靶标

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Breast-cancer is heterogeneous and consists of various groups with different biological characteristics. Innovative pharmacological approaches accounting for this heterogeneity are needed. The forty eight human Nuclear-Hormone-Receptors are ligand-dependent transcription-factors and are classified into Endocrine-Receptors, Adopted-Orphan-Receptors (Lipid-sensors and Enigmatic-Orphans) and Orphan-receptors. Nuclear-Receptors represent ideal targets for the design/synthesis of pharmacological ligands. We provide an overview of the literature available on the expression and potential role played by Lipid-sensors, Enigmatic-Orphans and Orphan-Receptors in breast-cancer. The data are complemented by an analysis of the expression levels of each selected Nuclear-Receptor in the PAM50 breast-cancer groups, following re-elaboration of the data publicly available. The major aim is to support the idea that some of the Nuclear-Receptors represent largely unexploited therapeutic-targets in breast-cancer treatment/chemo-prevention. On the basis of our analysis, we conclude that the Lipid-Sensors, NR1C3, NR1H2 and NR1H3 are likely to be onco-suppressors in breast-cancer. The Enigmatic-Orphans, NR1F1 NR2A1 and NR3B3 as well as the Orphan-Receptors, NR0B1, NR0B2, NR1D1, NR2F1, NR2F2 and NR4A3 exert a similar action. These Nuclear-Receptors represent candidates for the development of therapeutic strategies aimed at increasing their expression or activating them in tumor cells. The group of Nuclear-Receptors endowed with potential oncogenic properties consists of the Lipid-Sensors, NR1C2 and NR1I2, the Enigmatic-Orphans, NR1F3, NR3B1 and NR5A2, as well as the Orphan-Receptors, NR2E1, NR2E3 and NR6A1. These oncogenic Nuclear-Receptors should be targeted with selective antagonists, reverse-agonists or agents/strategies capable of reducing their expression in breast-cancer cells.
机译：乳腺癌是异质性的，由具有不同生物学特征的各种组组成。需要解决这种异质性的创新药理方法。四十八种人类核激素受体是依赖配体的转录因子，分为内分泌受体，采用的孤儿受体（脂质传感器和神秘的孤儿）和孤儿受体。核受体代表设计/合成药理配体的理想靶标。我们提供了有关脂质传感器，神秘孤儿和孤儿受体在乳腺癌中的表达及其潜在作用的文献综述。在重新整理可公开获得的数据之后，通过对PAM50乳腺癌组中每个选定核受体表达水平的分析来补充数据。主要目的是支持这样的想法，即某些核受体在乳腺癌治疗/化学预防中代表了很大程度上未被利用的治疗目标。根据我们的分析，我们得出结论，脂质传感器NR1C3，NR1H2和NR1H3可能是乳腺癌的抑癌药。神秘孤儿NR1F1 NR2A1和NR3B3以及孤儿受体NR0B1，NR0B2，NR1D1，NR2F1，NR2F2和NR4A3发挥相似的作用。这些核受体代表了旨在增加其在肿瘤细胞中的表达或激活它们的治疗策略的发展的候选者。具有潜在致癌特性的核受体组由脂质传感器NR1C2和NR1I2，神秘孤儿，NR1F3，NR3B1和NR5A2以及孤儿受体NR2E1，NR2E3和NR6A1组成。这些致癌核受体应靶向选择性拮抗剂，反向激动剂或能够降低其在乳腺癌细胞中表达的药物/策略。

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