Androgen-regulated gene expression in prostate cancer

Abstract

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.