Rizzi F, Bettuzzi S
Department of Experimental Medicine, University of Parma, Parma, Italy.
J Physiol Pharmacol. 2008 Dec;59 Suppl 9:265-74.
The biological function of Clusterin has been puzzling researchers for a long time since its first discovery and characterization in the early 80's. CLU plays important roles nearly in all most important biological phenomena including cell proliferation and apoptosis, as well as in many diseases including cancer. Now we know that the CLU gene encodes at least three protein forms with different sub-cellular localization and diverse biological functions. The molecular mechanism of production of these protein isoforms remains unclear. Recent data show that many of the previous hypotheses based on preliminary observations are no longer true. For instance, while alternative splicing of CLU mRNA has never been confirmed, the complex transcriptional regulation of CLU gene is now recognized to produce two distinct transcripts resulting from two independent transcriptional start sites. CLU expression was found deregulated in many type of tumours, including prostate cancer. Considering that prostate cancer is one of the major threats in veterans' life, as well as one of the main causes of cancer related death in western countries, we will also specifically address whether targeting CLU might pave the way for a novel therapeutic intervention against prostate cancer.
自80年代初首次发现并鉴定以来，簇集素的生物学功能一直困扰着研究人员。CLU几乎在所有最重要的生物学现象中都发挥着重要作用，包括细胞增殖和凋亡，以及在包括癌症在内的许多疾病中。现在我们知道，CLU基因编码至少三种具有不同亚细胞定位和多种生物学功能的蛋白质形式。这些蛋白质异构体的产生分子机制仍不清楚。最近的数据表明，许多基于初步观察的先前假设已不再成立。例如，虽然从未证实CLU mRNA的可变剪接，但现在认识到CLU基因的复杂转录调控会产生两种由两个独立转录起始位点产生的不同转录本。在包括前列腺癌在内的许多类型肿瘤中发现CLU表达失调。鉴于前列腺癌是退伍军人生命中的主要威胁之一，也是西方国家癌症相关死亡的主要原因之一，我们还将具体探讨靶向CLU是否可能为前列腺癌的新型治疗干预铺平道路。
