...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Frontiers in neuroendocrinology >Molecular pathogenesis of pituitary tumors.
【24h】

Molecular pathogenesis of pituitary tumors.

机译：垂体肿瘤的分子发病机制。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pituitary tumors are the result of a monoclonal outgrowth where the intrinsic genetic defects involve oncogenes, tumor suppressor genes (TSG), and most likely genes responsible for differentiation. In addition, hypothalamic and intrapituitary derived growth factors are imposed upon these aberrant cells, contributing to their growth characteristics. While histological examination will not identify those tumors likely to progress toward an invasive phenotype or those destined toward recurrence recent advances in the molecular pathology of these tumors holds significant promise for prediction of recurrence and the design of novel treatment strategies. Moreover, emerging data clearly indicate that different molecular mechanisms are involved in the pathogenesis of the various pituitary tumor subtypes. Until recently the gsp oncogene was the only oncogene significantly associated with pituitary tumors; however, emerging data have describe a role for PTTG and cyclin D1 in pituitary tumorigenesis. For known and putative TSG loci, allelic losses on the long arms of chromosomes 10, 11, and 13 are significantly associated with the transition from the noninvasive to the invasive and metastatic phenotype, while losses on chromosome 9p occur early in pituitary tumorigenesis. Studies of known TSG at these loci, including the menin gene and RB1, would suggest a limited role, if any, in pituitary tumors. However, loss of pRB is evident in a proportion of somatotropinomas but is not associated with allelic loss of an RB1 intragenic marker. The gene encoding p16/CDKN2A is neither deleted nor mutated in pituitary tumors; however, its associated CpG island is frequently methylated and is associated with a loss of p16 protein expression. Allelic losses on chromosome 9p, frequent methylation, and loss of p16 protein appear as early changes in nonfunctional tumors, whereas they are infrequent events in somatotropinomas. The functional consequence of enforced expression of p16/CDKN2A in the mouse corticotroph cell line AtT20 has shown that it is responsible for a profound reduction in cell proliferation and the mechanism is a G(1) arrest, mimicking the in vivo role of this cell cycle regulator in most tissues. The combined data from several groups show that the allelic losses reported at known TSG loci are not accompanied by mutation in the retained allele. However, since abnormal methylation patterns may precede and predispose toward genetic instability this could account for the allelic losses on these chromosomes. Equally, since DNA methylation may lead to reduced expression of a gene it might also account for the reduced expression of as yet unidentified TSGs implicated in pituitary tumorigenesis. Collectively these studies hold significant promise as markers predictive of tumor behavior and point to novel treatment strategies, which may include the reactivation of TSGs that are intact but silenced through epigenetic mechanisms. Copyright 2000 Academic Press.
机译：垂体瘤是单克隆生长的结果，其中固有的遗传缺陷涉及癌基因，抑癌基因（TSG）以及最有可能导致分化的基因。此外，下丘脑和脑垂体衍生的生长因子被施加到这些异常细胞上，从而有助于它们的生长特性。虽然组织学检查不能识别出可能发展成侵袭性表型的肿瘤或注定要复发的肿瘤，但是这些肿瘤的分子病理学的最新进展为预测复发和设计新的治疗策略提供了重要的希望。此外，新出现的数据清楚地表明，各种垂体肿瘤亚型的发病机理涉及不同的分子机制。直到最近，gsp致癌基因仍是唯一与垂体肿瘤显着相关的致癌基因。然而，新兴数据描述了PTTG和细胞周期蛋白D1在垂体肿瘤发生中的作用。对于已知的推定的TSG基因座，第10、11和13号染色体长臂上的等位基因缺失与从无创性向侵袭性和转移性表型的转变显着相关，而9p号染色体上的缺失发生在垂体肿瘤发生的早期。对这些基因座上已知的TSG的研究，包括Menin基因和RB1，将提示它们在垂体肿瘤中的作用有限。但是，pRB的丢失​​在一定比例的体质性肌瘤中很明显，但与RB1基因内标记的等位基因丢失无关。垂体肿瘤中编码p16 / CDKN2A的基因既不缺失也不突变。然而，其相关的CpG岛经常被甲基化，并与p16蛋白表达的丧失有关。 9p染色体上的等位基因缺失，频繁的甲基化和p16蛋白的缺失表现为非功能性肿瘤的早期变化，而在体质性肌瘤中则很少发生。小鼠皮质营养细胞AtT20中p16 / CDKN2A强制表达的功能结果表明，它可导致细胞增殖的大幅降低，其机制是G（1）阻滞，模仿此细胞周期的体内作用大多数组织中的调节剂。来自几组的综合数据显示，在已知的TSG基因座报道的等位基因缺失并没有伴随着保留等位基因的突变。但是，由于异常甲基化模式可能先于遗传不稳定性而趋于遗传不稳定性，因此可以解释这些染色体上的等位基因缺失。同样，由于DNA甲基化可能导致基因表达降低，因此它也可以解释与垂体肿瘤发生有关的尚未鉴定的TSG的表达降低。总的来说，这些研究作为预测肿瘤行为的标志物具有广阔的前景，并指出了新颖的治疗策略，其中可能包括重新激活完整但通过表观遗传机制沉默的TSG。版权所有2000学术出版社。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号