Cude K J, Dixon S C, Guo Y, Lisella J, Figg W D
Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA.
J Mol Med (Berl). 1999 May;77(5):419-26. doi: 10.1007/s001090050372.
The action of androgens in the development and growth of prostate carcinomas is well documented. The androgen receptor (AR) facilitates androgen-induced regulation of genes involved in cellular proliferation and differentiation. Since the early 1940s androgen ablation has been the cornerstone of treatment for metastatic prostate cancer. Although initially highly effective, hormonal therapy is not curative, and resistant disease will ultimately prevail. Mutations that alter AR conformation, function, and regulation may provide a selective growth advantage for subpopulations of cells within the tumor that are then able to proliferate in an androgen-deprived environment. Clinically, these mutations are important because they may lead to the growth of androgen-independent tumors and progression to a refractory state. Further characterization of AR mutations will lead to a more thorough understanding of their role in the development of prostate carcinomas. This information, in addition to discovering which genes are regulated by the AR, can aid in the future development of more effective pharmacotherapy for prostate cancer.
雄激素在前列腺癌发生和发展过程中的作用已有充分记录。雄激素受体（AR）促进雄激素诱导的对参与细胞增殖和分化的基因的调控。自20世纪40年代初以来，雄激素剥夺一直是转移性前列腺癌治疗的基石。尽管激素疗法最初非常有效，但它并不能治愈疾病，最终耐药性疾病会占上风。改变AR构象、功能和调控的突变可能为肿瘤内的细胞亚群提供选择性生长优势，这些细胞亚群随后能够在雄激素剥夺的环境中增殖。在临床上，这些突变很重要，因为它们可能导致雄激素非依赖性肿瘤的生长并进展到难治状态。对AR突变的进一步表征将有助于更全面地了解它们在前列腺癌发生中的作用。除了发现哪些基因受AR调控外，这些信息还可以帮助未来开发更有效的前列腺癌药物治疗方法。
