Debes Jose D, Tindall Donald J
Department of Urology, Rochester, MN 55905, USA.
Cancer Lett. 2002 Dec 10;187(1-2):1-7. doi: 10.1016/s0304-3835(02)00413-5.
Prostate cancer (PCa) is the leading diagnosed malignancy in men in western countries. The relationship between androgens and the androgen receptor (AR) has been studied extensively in PCa. Plasma levels of androgens show variations between different populations, and in many cases this correlates with PCa susceptibility. Indeed, exposure of the fetus to higher androgen concentrations appears to be a risk factor for PCa. The AR is present in the majority of PCa, and its activation by androgens leads to different proliferative, apoptotic and angiogenic events. These events are in turn mediated by dysregulation of cyclin-dependent kinases, apoptotic factors and even mutations in the AR. Although androgen ablation has been the mainstay non-surgical treatment for this disease, most tumors will eventually become refractory to treatment. Different cellular mechanisms appear to be involved in the androgen-independent progression of PCa, including cytokine and growth factor-mediated activation of the AR as well as neuroendocrine differentiation. Thus, an understanding of the cellular mechanisms involved in androgen action may lead to better therapeutic targets for PCa.
前列腺癌（PCa）是西方国家男性中最常被诊断出的恶性肿瘤。在前列腺癌中，雄激素与雄激素受体（AR）之间的关系已得到广泛研究。不同人群的血浆雄激素水平存在差异，在许多情况下，这与前列腺癌易感性相关。事实上，胎儿暴露于较高的雄激素浓度似乎是前列腺癌的一个危险因素。大多数前列腺癌中都存在雄激素受体，雄激素对其激活会导致不同的增殖、凋亡和血管生成事件。这些事件反过来又由细胞周期蛋白依赖性激酶、凋亡因子的失调甚至雄激素受体的突变介导。尽管雄激素剥夺一直是这种疾病的主要非手术治疗方法，但大多数肿瘤最终会对治疗产生耐药性。不同的细胞机制似乎参与了前列腺癌的雄激素非依赖性进展，包括细胞因子和生长因子介导的雄激素受体激活以及神经内分泌分化。因此，了解雄激素作用所涉及的细胞机制可能会为前列腺癌带来更好的治疗靶点。
