Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece.
Urol Oncol. 2012 Nov-Dec;30(6):752-61. doi: 10.1016/j.urolonc.2010.03.013. Epub 2010 Jun 26.
Prostate cancer is the most common carcinoma in the male population. In its initial stage, the disease is androgen-dependent and responds therapeutically to androgen deprivation treatment but it usually progresses after a few years to an androgen-independent phase that is refractory to hormonal manipulations. The proteasome is a multi-unit protease system that regulates the abundance and function of a significant number of cell proteins, and its inhibition results in cancer cell growth inhibition and apoptosis and is already exploited in the clinic with the use of proteasome inhibitor bortezomib in multiple myeloma. In order to be recognized by the proteasome, a target protein needs to be linked to a chain of the small protein ubiquitin. In this paper, we review the role of ubiquitin-proteasome system (UPS) in androgen receptor-dependent transcription as well as in the castration resistant stage of the disease, and we discuss therapeutic opportunities that UPS inhibition offers in prostate cancer.
前列腺癌是男性人群中最常见的癌种。在疾病早期，它依赖于雄激素，并且对雄激素剥夺治疗有治疗反应，但通常在几年后进展为雄激素非依赖性阶段，对激素治疗产生抵抗。蛋白酶体是一种多亚单位的蛋白酶系统，调节大量细胞蛋白的丰度和功能，其抑制导致癌细胞生长抑制和凋亡，并且已经在临床上使用蛋白酶体抑制剂硼替佐米治疗多发性骨髓瘤。为了被蛋白酶体识别，靶蛋白需要与一条小蛋白泛素的链相连。在本文中，我们综述了泛素-蛋白酶体系统（UPS）在雄激素受体依赖性转录以及疾病去势抵抗阶段中的作用，并讨论了 UPS 抑制在前列腺癌中提供的治疗机会。
