Heaney A P, Melmed S
Department of Medicine, Cedars-Sinai Research Institute, UCLA School of Medicine 90048, USA.
Baillieres Best Pract Res Clin Endocrinol Metab. 1999 Oct;13(3):367-80. doi: 10.1053/beem.1999.0028.
Although pituitary tumours are common monoclonal neoplasms, they rarely metastasize outside the pituitary fossa, even though they cause considerable morbidity and mortality. Many molecular events underlying pituitary tumourigenesis have been elucidated in recent years, but no clear tumour marker has emerged that assists clinical decision-making with regard to appropriate therapy. Activating mutations and a loss of inactivating mutations, together with hypothalamic hormones, circulating hormones, growth factors and cytokines, co-operatively ensure the inexorable expansion of the initial mutated pituitary cell clone. We have recently described a novel oestrogen-regulated activating oncogene, pituitary tumour transforming gene (PTTG), which is potently transforming in vitro and in vivo, regulates basic fibroblast growth factor secretion and inhibits chromatid separation. In experimental animal pituitary tumour models, increased PTTG expression occurs early in cell transformation (from normal to hyperplastic cell), PTTG overexpression being observed in 99% of pituitary tumours. PTTG presents an attractive target for designing subcellular pituitary tumour therapy, and an increased understanding of its role and that of other genetic events in pituitary tumorigenesis may provide novel approaches to pituitary tumour management.
尽管垂体肿瘤是常见的单克隆性肿瘤，但它们很少转移至垂体窝外，即便它们会导致相当高的发病率和死亡率。近年来，许多垂体肿瘤发生的分子事件已被阐明，但尚未出现明确的肿瘤标志物来辅助关于合适治疗的临床决策。激活突变和失活突变的缺失，连同下丘脑激素、循环激素、生长因子和细胞因子，共同确保了最初突变的垂体细胞克隆的不可阻挡的扩张。我们最近描述了一种新的雌激素调节的激活癌基因，垂体肿瘤转化基因（PTTG），它在体外和体内均具有强大的转化能力，调节碱性成纤维细胞生长因子的分泌并抑制染色单体分离。在实验动物垂体肿瘤模型中，PTTG表达增加在细胞转化早期（从正常细胞到增生细胞）就会出现，在99%的垂体肿瘤中观察到PTTG过表达。PTTG是设计垂体肿瘤亚细胞治疗的一个有吸引力的靶点，对其在垂体肿瘤发生中的作用以及其他遗传事件的作用的进一步了解可能会为垂体肿瘤的管理提供新的方法。
