Molecular Oncology Laboratory MOL. Departamento de Fisioloxia, Facultade de Medicina and Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS). Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS). Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Sci Rep. 2017 Oct 11;7(1):12991. doi: 10.1038/s41598-017-13408-x.
Oncogene-induced senescence (OIS) is a complex process, in which activation of oncogenic signals during early tumorigenesis results in a high degree of DNA replication stress. The ensuing response to the DNA damage produces a permanent G1 arrest that prevents unlimited cell proliferation and lessens the development of tumours. However, despite the role of OIS in the proliferative arrest resulting from an activating oncogenic-lesion has obtained wide support, there is also evidence indicating that cells may overcome oncogene-induced senescence under some circumstances. In this study, we have investigated the possibility that some of the assumptions on the role of DNA damage response (DDR) in triggering OIS may depend on the fact that most of the available data were obtained in mouse embryo fibroblast. By comparing the degree of OIS observed in mouse embryo fibroblasts (MEF) and mouse embryo astrocytes (MEA) obtained from the same individuals we have demonstrated that, despite truthful activation of DDR in both cell types, significant levels of OIS were only detected in MEF. Therefore, this uncoupling between OIS and DDR observed in astrocytes supports the intriguingly possibility that OIS is not a widespread response mechanism to DDR.
癌基因诱导的衰老（OIS）是一个复杂的过程，在早期肿瘤发生过程中，癌基因信号的激活导致高度的 DNA 复制应激。随之而来的对 DNA 损伤的反应产生了一个永久性的 G1 期阻滞，阻止了无限的细胞增殖，并减少了肿瘤的发展。然而，尽管 OIS 在由激活的致癌损伤导致的增殖阻滞中的作用得到了广泛的支持，但也有证据表明，在某些情况下，细胞可能会克服癌基因诱导的衰老。在这项研究中，我们研究了这样一种可能性，即在触发 OIS 方面，对 DNA 损伤反应（DDR）的一些假设可能取决于这样一个事实，即大多数可用的数据都是在小鼠胚胎成纤维细胞中获得的。通过比较从同一个体获得的小鼠胚胎成纤维细胞（MEF）和小鼠胚胎星形胶质细胞（MEA）中观察到的 OIS 程度，我们证明，尽管两种细胞类型中 DDR 都被真实地激活，但只有在 MEF 中才能检测到显著水平的 OIS。因此，星形胶质细胞中观察到的 OIS 和 DDR 之间的这种解耦支持了一个有趣的可能性，即 OIS 不是对 DDR 的广泛反应机制。
