Estrogens and prostate cancer: etiology, mediators, prevention, and management.
Estrogens and prostate cancer: etiology, mediators, prevention, and management.
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DOI：
10.1016/j.ecl.2011.05.002
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发表时间：
2011-09
影响因子：
4.5
通讯作者：
Leung, Yuet-Kin
中科院分区：
文献类型：
--
作者：
Ho, Shuk-Mei;Lee, Ming-Tsung;Lam, Hung-Ming;Leung, Yuet-Kin
关键词：
激素与前列腺癌发病机制之间的关系已被广泛研究。激素前列腺癌治疗的所有主要目标都是基于雄激素的负作用。最近的流行病学和实验数据清楚地指出了雌激素在前列腺癌发生和发展中的关键作用。种族和地理差异以及年龄相关的雌激素合成和代谢变化，通过增加循环雌激素与雄激素的比例、性激素结合球蛋白的合成和芳香化酶活性，降低雄激素糖醛酸化和组织生物活性，对病因有重要影响。成年期促进细胞异常生长、逃避细胞凋亡、增加氧化应激和炎症、增加脂肪和对遗传毒性致癌物的生物激活是雌激素致癌性的可能机制，而早期通过表观遗传学的“雌激素印记”也决定了前列腺癌的风险。虽然已知雌激素的作用是由两种雌激素受体（ER）亚型（ERα和ERβ）的基因组作用介导的，但其他非典型介质，包括不同的ERβ亚型、膜和线粒体ER以及G蛋白偶联受体30，可能具有与经典ER作用不同的主要作用。这些新发现引起了公众和医学界对雌激素和抗雌激素作为单一和辅助治疗和预防前列腺癌方案的新兴趣。本文综述了不同雌激素/抗雌激素/雌激素模拟物如何促进前列腺癌的发生，不同雌激素介质在这一过程中的作用，以及新的雌激素/抗雌激素化合物作为预防和治疗前列腺癌的靶向治疗的潜力。
The relationship between hormones and the pathogenesis of prostate cancer (PCa) has been studied extensively. All the mainstay targets for hormonal PCa therapies are based on negating androgen action. Recent epidemiologic and experimental data have clearly pinpointed the key roles of estrogens in PCa development and progression. Racial and geographical differences, as well as age-associated changes, in estrogen synthesis and metabolism contribute significantly to the etiology by increasing the ratio of circulating estrogen to androgen, sex hormone binding globulin synthesis, and aromatase activity and reducing androgen glucuronidation and tissue bioactivation. Promotion of aberrant cell growth, evasion of apoptosis, increased oxidative stress and inflammation, and gains in adiposity and bioactivation to genotoxic carcinogens during adulthood are probable mechanisms of estrogen carcinogenicity, while “estrogen imprinting” via epigenetics in early-life also determines PCa risk. Although the effects of estrogens are known to be mediated by genomic actions of the two estrogen receptor (ER) subtypes (ERα and ERβ), other non-canonical mediators, including the different ERβ isoforms, membrane and mitochondrial ERs, and G protein-coupled receptor 30, may have major actions diverging from classical ER actions. These new discoveries have led to renewed interest among the public and the medicinal field in estrogens and antiestrogens as singular and adjuvant PCa treatment and prevention regimens. This review summarizes current knowledge on how different estrogens/antiestrogens/estrogen mimics contribute to prostate carcinogenesis, the roles of the different mediators of estrogen in the process, and the potentials of new estrogenic/antiestrogenic compounds as targeted therapies for prevention and treatment of PCa.
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