Proteomics of androgen receptor co-regulators in prostate cancer
Summary
The androgen receptor (AR) is a ligand-dependent transcription factor. Binding
of androgens induces a conformational change and subsequently binding of the
receptor to androgen receptor elements (ARE) on the genomic DNA. AR activity
and specificity is additionally modulated by co-regulators that are recruited upon
ligand binding. So far, the precise role of co-regulators in mediating AR function
in different state in growth, aging, development and diseases is poorly
understood. Furthermore, studies have shown that post-translational
modification of the AR can affect AR activity. Androgen receptor is also one of the
driving forces of prostate cancer. Therefore detail knowledge about the function
of AR co-regulators is of urgent need.
Once we know which co-regulators are essential for cancer development, one
option to treat the cancer cells will be inhibition of the AR-co-regulator
interaction. A designed molecule or mini-protein can be used to change the
conformation of AR in the way it does not recruit that particular co-regulator/s.
The inhibition of the complex formation can be later checked by native MS.
Since up regulation of AR activity is likely the cause of prostate cancer, another
possible method to treat prostate cancer can be via inhibition of enzyme activity
inherits AR modifications such as phosphorylase.
In this report we describe an efficient proteomic analysis for the identification of
novel AR complexes in stroma and epithelium of normal and malignant prostate
cells.