The androgen receptor in prostate cancer

The androgen receptor is a member of the family of nuclear receptors. In its activated form as an androgen receptor ligand complex (the ligand can either be testosterone or 5a-dihydrotestosterone), the androgen receptor is able to regulate a specific expression of target genes. The androgen receptor is expressed at high levels in male reproductive tissues. Mutations in the androgen receptor gene are the molecular cause of the androgen insensitivity syndrome, which is characterized by an aberrant male or an apparently female phenotype. Expansion of a CAG-repeat, encoding a polymorphic glutamine stretch is the cause of a rare motor neuron disease (Kennedy's disease). Hormonal therapy is the treatment of choice for metastatic prostate cancer. Hormone refractory prostate tumors in general still express androgen receptor. In a proportion of the late stage prostate tumors, somatic mutations in the androgen receptor gene have been described. Mutations can result in diminished ligand specificity of the androgen receptor. Furthermore, it has been hypothesized that ligand independent mechanisms can also be involved in androgen receptor activation.