Endocrine Abstracts

The androgen receptor (AR) is a multidomain transcription factor consisting of an aminoterminal domain (NTD), a DNA binding domain (DBD) and a ligand binding domain (LBD). Binding of androgens marks the start of a sequence of intra- and interdomain communications, DNA binding, coregulator recruitment and gene activation. Besides the DBD-mediated dimerization on the DNA, there is a functionally relevant N/C interaction. The contribution of the intra- and intermolecular N/C inte...

Enzalutamide (Enza) is a second-generation antiandrogen currently used in the clinic for treatment of metastatic prostate cancer. It significantly prolonged survival of men with metastatic castration resistant prostate cancer after chemotherapy by a median of 4.8 months in comparison to the placebo group. However, in a subset of patient’s beneficial effect of Enza cannot be observed, while others who initially respond eventually develop resistance towards the treatment. U...

The importance of the androgen receptor (AR) in the development and maintenance of the male phenotype is demonstrated by patients with androgen insensitivity syndrome (AIS). These patients carry germline mutations in the AR and display a mild to complete intersex phenotype. The AR belongs to the subfamily of steroid receptors, which need to form homodimers to execute their role as transcription factors. For estrogen receptors, dimerization via the DNA-binding domains as well a...

Clinical features of the primary prostate tumor remain insufficient for clinicians to accurately define patients at highest risk of developing metastases. However, the primary tumor is the source of these metastases, and thus should contain information on its metastatic potential. We hypothesized that the combination of a primary tumor’s copy number alterations (CNAs) and genome-wide transcriptome information would give us more insight in the biology of metastases-prone l...