Trapman J, Cleutjens K B
Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
Semin Cancer Biol. 1997 Feb;8(1):29-36. doi: 10.1006/scbi.1997.0050.
Androgen-regulated gene expression is mediated by the ligand-activated androgen receptor. Androgen receptor target genes contain in the regulatory regions one or more androgen response elements. Development of the male urogenital tract, including the prostate, depends on an activated androgen receptor. Similarly, growth of the majority of prostate cancers is androgen-dependent. Therefore, endocrine therapy, aimed at inhibition of androgen receptor functioning, has been applied for many years. However, during therapy, apparently androgen receptor independent cancers continue to grow. In general, these tumors still express the androgen receptor, suggesting a functional role of the androgen receptor. In a proportion of late stage prostate tumors, mutations and amplification of the androgen receptor gene have been found. Additionally, it has been hypothesized that ligand-independent androgen receptor activation can be involved in hormone refractory prostate cancer.
雄激素调节的基因表达由配体激活的雄激素受体介导。雄激素受体靶基因在调控区域含有一个或多个雄激素反应元件。包括前列腺在内的男性泌尿生殖道的发育依赖于激活的雄激素受体。同样，大多数前列腺癌的生长也依赖雄激素。因此，旨在抑制雄激素受体功能的内分泌治疗已应用多年。然而，在治疗期间，明显雄激素受体非依赖性的癌症仍在继续生长。一般来说，这些肿瘤仍表达雄激素受体，提示雄激素受体具有功能性作用。在一部分晚期前列腺肿瘤中，已发现雄激素受体基因的突变和扩增。此外，有人推测非配体依赖性雄激素受体激活可能与激素难治性前列腺癌有关。
