MECHANISMS FOR PITUITARY TUMORIGENESIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。虽然垂体瘤是常见的单克隆性肿瘤，但很少会转移到垂体窝以外，但会引起相当大的发病率和死亡率。近年来，许多潜在的垂体肿瘤发生的分子事件已被阐明，但还没有明确的肿瘤标志物出现，以帮助临床决定适当的治疗。我们最近报道了一种新的雌激素调节的激活癌基因，即垂体肿瘤转化基因(PTTG)，它在体内和体外都有很强的转化作用，可以调节碱性成纤维细胞生长因子(BFGF)的分泌，并抑制染色单体的分离。在实验性动物垂体瘤模型中，PTTG表达增加发生在细胞转化的早期(正常？在99%的垂体瘤中可见PTTG过表达。PTTG是设计亚细胞垂体瘤治疗的一个有吸引力的靶点，对其作用和其他基因事件在垂体瘤发生中的作用的深入了解可能为垂体瘤的治疗提供新的途径。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although pituitary tumors are common monoclonal neoplasms, they rarely metastasize outside the pituitary fossa, but cause considerable morbidity and mortality. Many molecular events underlying pituitary tumorigenesis have been elucidated in recent years, but no clear tumor marker has emerged which assists clinical decisions regarding appropriate therapy. We have recently described a novel estrogen-regulated activating oncogene, Pituitary Tumor Transforming Gene (PTTG), which is potently transforming in vitro and in vivo, regulates basic fibroblast growth factor (bFGF) secretion and inhibits chromatid separation. In experimental animal pituitary tumor models, increased PTTG expression occurs early in cell transformation (normal ? hyperplastic cell) and PTTG overexpression was observed in 99% of pituitary tumors. PTTG presents an attractive target for designing subcellular pituitary tumor therapy and increased understanding of its role and that of other genetic events in pituitary tumorigenesis may provide novel approaches to pituitary tumor management.