Dehm Scott M, Tindall Donald J
Departments of Urology and Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Mol Endocrinol. 2007 Dec;21(12):2855-63. doi: 10.1210/me.2007-0223. Epub 2007 Jul 17.
The androgen receptor (AR) is a nuclear receptor transcription factor that mediates the cellular actions of androgens, the male sex steroids. Androgen-dependent tissues, such as the prostate, rely on androgen action for their development as well as their maintenance in adulthood. This requirement is exploited during systemic therapy of prostate cancer, which is initially an androgen-dependent disease. Indeed, androgen ablation, which prevents the production or blocks the action of androgens, inhibits prostate cancer growth. Invariably, the disease recurs with a phenotype resistant to further hormonal manipulations. However, this so-called androgen depletion-independent prostate cancer remains dependent on a functional AR for growth. Many studies have focused on the mechanistic and structural basis of AR activation with the important goal of understanding how the AR is activated at this stage of the disease. In this review, we summarize how these studies have revealed important functional domains in the AR protein and have provided initial clues to their role in prostate cancer development and progression. A comprehensive understanding of the role and functional relationships between these AR domains could lead to the development of novel AR-directed therapies for prostate cancer.
雄激素受体（AR）是一种核受体转录因子，介导雄激素（男性甾体性激素）的细胞作用。雄激素依赖组织，如前列腺，其发育以及成年期维持均依赖雄激素作用。前列腺癌全身治疗利用了这一需求，前列腺癌最初是一种雄激素依赖型疾病。事实上，雄激素消融（阻止雄激素产生或阻断其作用）可抑制前列腺癌生长。该疾病总是会复发，且表现出对进一步激素操作耐药的表型。然而，这种所谓的雄激素非依赖型前列腺癌的生长仍依赖功能性AR。许多研究聚焦于AR激活的机制和结构基础，其重要目标是了解在疾病的这一阶段AR是如何被激活的。在本综述中，我们总结了这些研究如何揭示AR蛋白中的重要功能结构域，并为它们在前列腺癌发生和进展中的作用提供了初步线索。全面了解这些AR结构域之间的作用和功能关系可能会促成针对前列腺癌的新型AR导向疗法的开发。
