文章:
癌细胞的核结构
Nuclear structure in cancer cells
原文发布日期:2004-09-01
DOI: 10.1038/nrc1430
类型: Review Article
开放获取: 否
要点:
- The architecture of cell nuclei is often altered in cancer cells. Specific tumour types are associated with characteristic alterations, and these provide an important diagnostic feature.
- The nuclear matrix participates in the spatial organization of the genome and other nuclear components. The protein composition of the nuclear matrix is altered in tumour cells and these changes might be useful tumour markers.
- Characteristic changes of nuclear shape and of chromatin texture can be induced in normal cells in vitro by oncogene activation. In vitro models will help to unravel the mechanisms by which oncogenes induce these tumour-specific nuclear changes and how these changes affect gene regulation.
- Chromosome territories and gene loci display characteristic spatial arrangements in cell nuclei, and these have an important role in the generation of diagnostically significant translocations associated with human malignancies.
- Structural alterations in tumour cells also include changes in nucleoli and the appearance of the perinucleolar compartment. These might be useful diagnostic markers in combination with automated imaging and image analysis.
- The promyelocytic leukaemia (PML) protein, an essential component of PML bodies, is mislocalized in leukaemic cells of patients with acute promyelocytic leukaemia, leading to the disruption of PML bodies. Treatment with anticancer drugs leads to the reassembly of PML bodies and a reversion of the malignant phenotype.
- High-throughput nuclear-structure-based assays to screen drugs for their ability to revert malignancy-associated nuclear changes might identify new therapeutics.
要点翻译:
- 癌细胞核的结构常发生改变。特定肿瘤类型与特征性改变相关,这些改变提供了重要的诊断依据。
- 核基质参与基因组及其他核成分的空间组织。肿瘤细胞中核基质的蛋白质组成发生改变,这些变化可能成为有用的肿瘤标志物。
- 癌基因激活可在体外诱导正常细胞出现核形态和染色质结构的特征性改变。体外模型将有助于揭示癌基因诱导这些肿瘤特异性核改变的机制,以及这些改变如何影响基因调控。
- 染色体领域和基因位点在细胞核中呈现特征性空间排列,这对人类恶性肿瘤相关诊断性易位的产生具有重要作用。
- 肿瘤细胞的结构改变还包括核仁的变化以及核仁周区室的出现。结合自动化成像和图像分析技术,这些可能成为有用的诊断标志物。
- 早幼粒细胞白血病(PML)蛋白作为PML核体的重要组成部分,在急性早幼粒细胞白血病患者的白血病细胞中定位异常,导致PML核体解体。抗癌药物治疗可促使PML核体重组,并使恶性表型发生逆转。
- 基于核结构的高通量检测方法可用于筛选能够逆转恶性肿瘤相关核改变的药物,这可能为发现新疗法提供途径。
英文摘要:
Nuclear architecture — the spatial arrangement of chromosomes and other nuclear components — provides a framework for organizing and regulating the diverse functional processes within the nucleus. There are characteristic differences in the nuclear architectures of cancer cells, compared with normal cells, and some anticancer treatments restore normal nuclear structure and function. Advances in understanding nuclear structure have revealed insights into the process of malignant transformation and provide a basis for the development of new diagnostic tools and therapeutics.
摘要翻译:
核结构——染色体及其他核组分的空间排布——为核内多种功能过程的组织和调控提供了框架。与正常细胞相比,癌细胞的核结构具有特征性差异;某些抗癌治疗可恢复正常的核结构与功能。对核结构认识的进展揭示了恶性转化过程的机制,并为新诊断工具和治疗方法的开发奠定了基础。
原文链接:
Nuclear structure in cancer cells