Nelles Jason L, Hu Wen-Yang, Prins Gail S
Department of Urology, University of Illinois at Chicago, 820 South Wood Street, MC 955, Chicago, IL 60612, USA.
Expert Rev Endocrinol Metab. 2011 May;6(3):437-451. doi: 10.1586/eem.11.20.
Early work on the hormonal basis of prostate cancer focused on the role of androgens, but more recently estrogens have been implicated as potential agents in the development and progression of prostate cancer. In this article, we review the epidemiological, laboratory and clinical evidence that estrogen may play a causative role in human prostate cancer, as well as rodent and grafted in vivo models. We then review recent literature highlighting potential mechanisms by which estrogen may contribute to prostate cancer, including estrogenic imprinting and epigenetic modifications, direct genotoxicity, hyperprolactinemia, inflammation and immunologic changes, and receptor-mediated actions. We discuss the work performed so far separating the actions of the different known estrogen receptors (ERs), ERα and ERβ, as well as G-protein-coupled receptor 30 and their specific roles in prostate disease. Finally, we predict that future work in this field will involve more investigations into epigenetic changes, experiments using new models of hormonal dysregulation in developing human prostate tissue, and continued delineation of the roles of the different ER subtypes, as well as their downstream signaling pathways that may serve as therapeutic targets.
早期关于前列腺癌激素基础的研究聚焦于雄激素的作用，但最近雌激素被认为是前列腺癌发生和进展的潜在因素。在本文中，我们综述了流行病学、实验室及临床证据，表明雌激素可能在人类前列腺癌中起致病作用，同时也涉及啮齿动物和体内移植模型。然后我们回顾了近期文献，突出了雌激素可能促进前列腺癌的潜在机制，包括雌激素印记和表观遗传修饰、直接基因毒性、高催乳素血症、炎症和免疫变化以及受体介导的作用。我们讨论了目前为区分不同已知雌激素受体（ERs）、ERα和ERβ以及G蛋白偶联受体30的作用及其在前列腺疾病中的特定作用所开展的工作。最后，我们预测该领域未来的工作将包括对表观遗传变化进行更多研究、利用发育中的人类前列腺组织激素失调新模型开展实验，以及继续阐明不同ER亚型的作用及其可能作为治疗靶点的下游信号通路。
