Marica Cariello, Simon Ducheix, Salwan Maqdasy, Silvère Baron, Antonio Moschetta, Jean-Marc A Lobaccaro
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引用次数: 0
摘要
雄激素和雄激素受体(AR,NR3C4)显然在前列腺癌的发展过程中起着至关重要的作用。此外,代谢紊乱与前列腺癌发病风险之间的联系近年来也逐渐显现出来。有趣的是,LXRα/NR1H3 和 LXRβ/NR1H2(以及 FXRα/NR1H4 和 SHP/NR0B2)等 "脂质 "核受体被描述为降低脂质代谢,而 AR 则增加脂质代谢。此外,这些前孤儿核受体还能调节雄激素水平并调节 AR 的活性。因此,发现这些受体参与前列腺的生理过程也就不足为奇了。这篇综述主要探讨肝X受体(LXRs)、法呢样X受体(FXR)和小异二聚体伙伴(SHP)在前列腺生理中的作用,以及它们通过调节前列腺内活性雄激素水平干扰雄激素调控途径的能力。通过使用前列腺癌细胞系、缺乏这些核受体的小鼠和人体组织库,一些作者指出了以这些受体为药物靶点的可能性。这些数据为开发新药开辟了一个新的研究领域,新药可以克服前列腺癌患者常见的阉割抵抗现象。
LXRs, SHP, and FXR in Prostate Cancer: Enemies or Ménage à Quatre With AR?
Androgens and androgen receptor (AR, NR3C4) clearly play a crucial role in prostate cancer progression. Besides, the link between metabolic disorders and the risk of developing a prostate cancer has been emerging these last years. Interestingly, "lipid" nuclear receptors such as LXRα/NR1H3 and LXRβ/NR1H2 (as well as FXRα/NR1H4 and SHP/NR0B2) have been described to decrease the lipid metabolism, while AR increases it. Moreover, these former orphan nuclear receptors can regulate androgen levels and modulate AR activity. Thus, it is not surprising to find such receptors involved in the physiology of prostate. This review is focused on the roles of liver X receptors (LXRs), farnesoid X receptor (FXR), and small heterodimeric partner (SHP) in prostate physiology and their capabilities to interfere with the androgen-regulated pathways by modulating the levels of active androgen within the prostate. By the use of prostate cancer cell lines, mice deficient for these nuclear receptors and human tissue libraries, several authors have pointed out the putative possibility to pharmacologically target these receptors. These data open a new field of research for the development of new drugs that could overcome the castration resistance in prostate cancer, a usual phenomenon in patients.