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        Proteomics of androgen receptor co-regulators in prostate cancer

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        Proteomics of AR co-regulators in prostate cancer.pdf (1.688Mb)
        Publication date
        2010
        Author
        Goodarzifard, M.
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        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.
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        https://studenttheses.uu.nl/handle/20.500.12932/4577
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