Endocrine Abstracts

The androgen receptor (AR) is a steroid-hormone receptor that plays a crucial role in the normal development of male reproductive tissues. Its high expression and/or relaxation of its regulation are strongly implicated in prostate cancer (PCa). Androgen binding induces conformational changes of AR that influence its subcellular localization, interactions with other proteins, DNA binding and transcriptional activity. Androgen dependent is also AR(S81) phosphorylation. Phosphorylation of AR at position of serine 81 was first associated with CDK1, in another study, it was found that CDK9 can mediate AR(S81) phosphorylation as well. In both studies, experiments were performed with pan-selective CDK inhibitors such as roscovitine or flavopiridol, therefore we decided to elucidate effects of CDKs on AR phosphorylation at serine 81 in detail. In our study, we transiently silenced CDK1, 2, 4, 7 and 9 by transfecting PCa cells with CDK-specific siRNA. Observed effect was compared with changes in AR phosphorylation at S81 after chemical inhibition using CDK inhibitors with confirmed selectivity against particular CDKs. According to our results, phosphorylation of AR at S81 can be mediated by several CDKs.

Funding: Czech Science Foundation (grant 15-17282Y).

Presenting Author: Zuzana Skrášková, Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Palacky University & Institute of Experimental Botany ASCR, Slechtitelu 27, 78371 Olomouc, Czech Republic. Email: [email protected]