Dipartimento di Medicina Sperimentale, Sezione di Biochimica, Biochimica Clinica e Biochimica dell'Esercizio Fisico, Università di Parma, Parma, Italy.
Endocr Relat Cancer. 2010 Jan 29;17(1):R1-17. doi: 10.1677/ERC-09-0140. Print 2010 Mar.
The biological functions of clusterin (CLU, also known as ApoJ, SGP2, TRPM-2, CLI) have been puzzling the researchers since its first discovery in the early 80's. We know that CLU is a single 9-exons gene expressing three protein forms with different sub-cellular localisations and diverse biological functions. Despite the many reports from many research teams on CLU action and its relation to tumourigenesis, contradictions in the data and alternative hypothesis still exist. Understanding the role of CLU in tumourigenesis is complicated not only by the existence of different protein forms but also by the changes of tumours over time and the selection pressures imposed by treatments such as hormone ablation or chemotherapy. This review focuses on recent discoveries concerning the role of CLU in prostate and breast cancer onset and progression. Although CLU acts primarily as a tumour suppressor in the early stages of carcinogenesis, consistent with its role in the involution of the prostate following castration, late stage cancer may overexpress CLU following chemotherapeutic drugs or hormonal ablation therapy. High expression of secreted or cytoplasmic CLU may represent a pro-survival stimulus because it confers increased resistance to killing by anti-cancer drugs or enhances tumour cell survival in specific niches.
CLU（也称为 ApoJ、SGP2、TRPM-2、CLI）的生物学功能自 80 年代初首次发现以来一直困扰着研究人员。我们知道 CLU 是一个单 9 外显子基因，表达三种具有不同亚细胞定位和不同生物学功能的蛋白质形式。尽管许多研究小组报告了 CLU 的作用及其与肿瘤发生的关系，但数据中的矛盾和替代假设仍然存在。CLU 在肿瘤发生中的作用不仅受到不同蛋白质形式的存在的影响，而且还受到肿瘤随时间的变化以及激素消融或化疗等治疗施加的选择压力的影响。这篇综述重点介绍了最近关于 CLU 在前列腺癌和乳腺癌发生和进展中的作用的发现。尽管 CLU 在致癌作用的早期主要作为肿瘤抑制因子发挥作用，这与它在去势后前列腺退化中的作用一致，但在化疗药物或激素消融治疗后，晚期癌症可能会过度表达 CLU。分泌型或细胞质 CLU 的高表达可能代表一种促生存刺激，因为它赋予了对抗癌药物杀伤的更高抗性，或增强了肿瘤细胞在特定小生境中的存活能力。
