Insulin-like growth factor, insulin-like growth factor-binding protein-4, and pregnancy-associated plasma protein-A gene expression in human granulosa cell tumors
Insulin-like growth factor, insulin-like growth factor-binding protein-4, and pregnancy-associated plasma protein-A gene expression in human granulosa cell tumors
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DOI：
10.1111/j.1525-1438.2006.00724.x
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发表时间：
2006-11-01
影响因子：
4.8
通讯作者：
Fuller, P. J.
中科院分区：
文献类型：
--
作者：
Alexiadis, M.;Mamers, P.;Fuller, P. J.
胰岛素样生长因子（IGF）系统在卵泡发生中起重要作用。它也被认为有助于许多癌症的发病机制，包括卵巢上皮癌。在人类卵泡中，主要的IGF是IGF-II，其作用由胰岛素样生长因子结合蛋白-4（IGFBP-4）、IGFBP-4蛋白酶和妊娠相关血浆蛋白-A（PAPP-A）调节。这些肽成分由发育中卵泡的颗粒细胞合成。本研究的目的是描述这些组成部分的IGF系统的表达在颗粒细胞瘤（GCT）的卵巢。在一组GCT中测定IGF-I、IGF-II、IGFBP-4和PAPP-A基因表达，并与正常卵巢和上皮性卵巢肿瘤中的水平进行比较。虽然IGF-I和IGF-II基因在GCT中表达，但水平低于其他组织组。IGFBP-4在GCT中的表达也较低，而PAPP-A基因在GCT中的表达最高。考虑到该信号系统在正常颗粒细胞中发挥的重要作用，这些发现是出乎意料的。总之，这些观察结果表明，IGF系统可能有一个有限的作用，GCT与PAPP-A subserving功能以外的IGFBP-4蛋白水解。
The insulin-like growth factor (IGF) system plays an important role in folliculogenesis. It is also thought to contribute to the pathogenesis of many cancers, including those of the ovarian epithelium. In the human follicle, the predominant IGF is IGF-II and its actions are modulated by insulin-like growth factor-binding protein-4 (IGFBP-4), the IGFBP-4 protease, and the pregnancy-associated plasma protein-A (PAPP-A). These peptide components are synthesized by the granulosa cells of the developing follicle. The aim of this study was to characterize the expression of these components of the IGF system in granulosa cell tumors (GCT) of the ovary. IGF-I, IGF-II, IGFBP-4, and PAPP-A gene expression was determined in a panel of GCT and compared to the levels in normal ovary and in epithelial ovarian tumors. Although both the IGF-I and IGF-II genes were expressed in the GCT, the levels were lower than in the other tissue groups. IGFBP-4 expression was also low in the GCT, whereas PAPP-A gene expression was highest in the GCT. These findings were unexpected given the prominent role this signaling system plays in normal granulosa cells. In conclusion, these observations suggest that the IGF system may have a limited role in the pathogenesis of GCT with PAPP-A subserving a function other than IGFBP-4 proteolysis.