The Role for Androgen Receptor Coactivators in PCA

There is an increasing research interest for AR cofactors in PCA. AR cofactors have either histone acetylase or deacetylase activity, therefore, they are classified as co-activators or co-repressors. Some observations in this field are controversial, especially those concerning AR-specific enhancement of activation. More work is needed to identify specific cofactors involved in PCA progression. Studies on AR cofactors were hampered because of a lack of appropriate antibodies.

We focused on the role of the cofactor CBP in carcinoma of the prostate (45). It potentiates activation of the AR by androgen and non-steroidal anti-androgens, hydroxyflutamide and bicalutamide. The effects on AR-induced activity by hydroxyflutamide were more pronounced that those stimulated by bicalutamide. These effects were observed in DU-145 and LNCaP cells with the wild-type and two mutant receptors. CBP is expressed in PCA cell lines LNCaP, PC-3, and DU-145, and also in clinical specimens. Regulation of CBP in PCA by peptide and steroid hormones is being investigated. In other studies, it was shown that the expression of the cofactor RAC3 correlates with tumor grade and stage (46). Interestingly, nuclear localization of the cofactor Tip60 is enhanced during androgen withdrawal (47). Gregory, et al. investigated the expression of AR cofactors in relapsed PCA and found that SRC 1 and TIF 2 are up-regulated (48).

It was suggested that the AR cofactor ARA70 is involved in potentiation of action of androgens and anti-androgens in PCA (49, 50). In studies with ARA70, there was no considerable difference in the extent of activation of the AR by hydroxyflutamide or bicalutamide, respectively.

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