Tfelt-Hansen Jacob, Kanuparthi Deepthi, Chattopadhyay Naibedya
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Clin Med Res. 2006 Jun;4(2):130-7. doi: 10.3121/cmr.4.2.130.
Pituitary tumor transforming gene (PTTG) is a newly discovered oncogene, and serves as a marker of malignancy grades in several forms of cancer, particularly endocrine malignancies such as pituitary adenomas. PTTG appears also to have a role in the genesis of some types of cancer. Also known as a human form of securin, PTTG is an anaphase inhibitor that prevents premature chromosome separation through inhibition of separase activity; hence, its degradation is required to start anaphase. Through this important function, PTTG participates in several key cellular events such as mitosis, cell cycle progression, DNA repair and apoptosis. The physiological importance of PTTG is indicated by the study of PTTG-null mice that have cell growth abnormalities in testis and pancreatic beta cells. Overexpression of PTTG has been observed in thyroid and colon cancers. In addition, 90% of pituitary adenomas overexpress PTTG, qualifying it as the best available marker for this disease. Although the exact mechanism is unknown, PTTG participates in the pathogenesis of various tumors, including pituitary tumors, by inducing aneuploidy and upregulating FGF-2, a potent mitogenic and angiogenic factor. Various growth factors, nuclear factors and hormones regulate PTTG expression in different tumor cells, which could be important to understand in order to obtain insight into the tumorigenic and tumor progression process. Here, we review the current knowledge of the biological and pathophysiological roles of PTTG.
垂体肿瘤转化基因（PTTG）是一种新发现的癌基因，在多种癌症尤其是内分泌恶性肿瘤（如垂体腺瘤）中作为恶性程度的标志物。PTTG似乎在某些类型癌症的发生中也起作用。PTTG也被称为人源形式的分离酶抑制蛋白，是一种后期抑制剂，通过抑制分离酶活性来防止染色体过早分离；因此，其降解是启动后期所必需的。通过这一重要功能，PTTG参与了有丝分裂、细胞周期进程、DNA修复和细胞凋亡等几个关键的细胞事件。对PTTG基因敲除小鼠的研究表明了PTTG的生理重要性，这些小鼠在睾丸和胰腺β细胞中存在细胞生长异常。在甲状腺癌和结肠癌中已观察到PTTG的过表达。此外，90%的垂体腺瘤过表达PTTG，使其成为该疾病目前最佳的可用标志物。尽管确切机制尚不清楚，但PTTG通过诱导非整倍体和上调FGF-2（一种强大的促有丝分裂和血管生成因子）参与包括垂体肿瘤在内的各种肿瘤的发病机制。各种生长因子、核因子和激素调节不同肿瘤细胞中PTTG的表达，了解这一点对于深入了解肿瘤发生和肿瘤进展过程可能很重要。在此，我们综述了目前关于PTTG生物学和病理生理学作用的知识。
