Yu Run, Melmed Shlomo
Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Front Horm Res. 2004;32:175-85. doi: 10.1159/000079044.
Herein we summarize the recent rapid advances in understanding the pituitary tumor transforming gene (PTTG) oncogene. Clinical studies reveal that PTTG-binding factor, fibroblast growth factor 2, and vascular endothelial growth factor are elevated in pituitary tumors, and mostly correlate with PTTG levels, also confirming the PTTG role in angiogenesis. PTTG overexpression disrupts mitosis and causes aneuploidy in single live cells and PTTG modulates p53 activity and p53 also mediates DNA damage-induced inhibition of PTTG transcription. Physiological functions of PTTG are revealed by PTTG-null mice who exhibit a variety of cell growth abnormalities including diabetes mellitus secondary to defective beta-cell proliferation. PTTG is therefore an oncogene for pituitary tumors and other neoplasia, and also involved in critical metabolic functions. Further studies are required to address mechanisms for these oncogenic and physiological functions, and more importantly, to understand conditions which determine the switch of PTTG from functioning physiologically to behaving as an oncogene.
在此,我们总结了在理解垂体肿瘤转化基因(PTTG)致癌基因方面最近取得的快速进展。临床研究表明,垂体肿瘤中PTTG结合因子、成纤维细胞生长因子2和血管内皮生长因子水平升高,且大多与PTTG水平相关,这也证实了PTTG在血管生成中的作用。PTTG的过表达会破坏有丝分裂并导致单个活细胞出现非整倍体,PTTG还可调节p53活性,而p53也介导DNA损伤诱导的PTTG转录抑制。PTTG基因敲除小鼠揭示了PTTG的生理功能,这些小鼠表现出多种细胞生长异常,包括因β细胞增殖缺陷继发的糖尿病。因此,PTTG是垂体肿瘤和其他肿瘤的致癌基因,并且还参与关键的代谢功能。需要进一步研究来阐明这些致癌和生理功能的机制,更重要的是,了解决定PTTG从发挥生理功能转变为致癌基因行为的条件。