Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
Cell Cycle. 2012 Sep 15;11(18):3415-20. doi: 10.4161/cc.21730. Epub 2012 Aug 16.
Hormone-dependent tumors are characterized by deregulated activity of specific steroid receptors, allowing aberrant expression of many genes involved in cancer initiation, progression and metastasis. In prostate cancer, the androgen receptor (AR) protein has pivotal functions, and over the years it has been the target of different drugs. AR is a nuclear receptor whose activity is regulated by a phosphorylation mechanism controlled by hormone and growth factors. Following phosphorylation, AR interacts with many cofactors that closely control its function. Among such cofactors, Pin1 is a peptidyl-prolyl isomerase that is involved in the control of protein phosphorylation and has a prognostic value in prostate cancer. In the present study, we demonstrate that ARSer81 is involved in the interaction with Pin1, and that this interaction is important for the transcriptional activity of AR. Since Pin1 expression positively correlates with tumor grade, our results suggest that Pin1 can participate in this process by modulating AR function.
激素依赖性肿瘤的特征是特定类固醇受体的活性失调，从而导致许多参与癌症起始、进展和转移的基因异常表达。在前列腺癌中，雄激素受体（AR）蛋白具有关键作用，多年来一直是不同药物的靶标。AR 是一种核受体，其活性受激素和生长因子控制的磷酸化机制调节。磷酸化后，AR 与许多共同因子相互作用，这些共同因子密切控制其功能。在这些共同因子中，Pin1 是一种肽脯氨酰顺反异构酶，参与蛋白质磷酸化的调控，在前列腺癌中具有预后价值。在本研究中，我们证明了 ARSer81 参与与 Pin1 的相互作用，并且这种相互作用对于 AR 的转录活性很重要。由于 Pin1 的表达与肿瘤分级呈正相关，我们的结果表明，Pin1 可以通过调节 AR 功能参与这一过程。
