Ahmad Nihal
Department of Dermatology, University of Wisconsin Comprehensive Cancer Center, Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53706, USA .
FASEB J. 2004 Jan;18(1):5-7. doi: 10.1096/fj.03-0848hyp.
Second only to skin cancer, cancer of the prostate gland (CaP) is the most commonly occurring cancer in American men. Existing treatment approaches and surgical intervention have been unable to effectively manage this dreaded cancer; therefore, efforts are ongoing to explore novel targets and strategies for the management of CaP. A complete understanding of the genetic control of the processes of cellular proliferation and programmed cell death, or "apoptosis," may provide the basis for the rational design of novel therapeutic strategies against CaP. Key regulators for the mitotic progression in mammalian cells are the polo-like kinases (Plks). The activity of Plk1 is elevated in tissues and cells with a high mitotic index, including cancer cells. An increasing body of evidence suggests that the level of Plk1 expression has prognostic value for predicting outcomes in patients with some cancers such as lung cancer, squamous cell carcinomas of the head and neck, melanomas, and ovarian and endometrial carcinomas. However, the role of Plk1 in CaP is not known. Here, a hypothesis is put forward that Plk 1 plays a critical role in the development of prostate cancer; and the silencing of Plk1 will result in elimination of human CaP cells via an inactivation of cyclin-dependent kinase 1 (Cdc2)/cyclin B 1-mediated mitotic arrest followed by apoptosis. A corollary to this hypothesis is that Plk1 could serve as a target for the intervention of CaP in humans. Therefore, if the hypothesis is tested to be true, it is conceivable that gene therapeutic approaches aimed at Plk1 or the pharmacological inhibitors of Plk1 may be developed for the treatment/management of CaP.
前列腺癌（CaP）是美国男性中第二常见的癌症，仅次于皮肤癌。现有的治疗方法和手术干预都无法有效应对这种可怕的癌症；因此，人们正在努力探索治疗CaP的新靶点和新策略。全面了解细胞增殖和程序性细胞死亡（即“凋亡”）过程的基因控制，可能为合理设计针对CaP的新治疗策略提供依据。哺乳动物细胞有丝分裂进程的关键调节因子是polo样激酶（Plks）。Plk1的活性在有丝分裂指数高的组织和细胞（包括癌细胞）中升高。越来越多的证据表明，Plk1的表达水平对预测某些癌症（如肺癌、头颈部鳞状细胞癌、黑色素瘤以及卵巢癌和子宫内膜癌）患者的预后具有重要价值。然而，Plk1在CaP中的作用尚不清楚。在此，我们提出一个假设，即Plk1在前列腺癌的发展中起关键作用；沉默Plk1将通过使细胞周期蛋白依赖性激酶1（Cdc2）/细胞周期蛋白B1介导的有丝分裂停滞失活，随后引发凋亡，从而导致人CaP细胞的消除。这个假设的一个推论是，Plk1可以作为人类CaP干预的靶点。因此，如果这个假设被证明是正确的，那么可以设想，针对Plk1的基因治疗方法或Plk1的药理学抑制剂可能会被开发用于CaP的治疗/管理。
