Abstract

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.

Details

Title
Uncoupling Oncogene-Induced Senescence (OIS) and DNA Damage Response (DDR) triggered by DNA hyper-replication: lessons from primary mouse embryo astrocytes (MEA)
Author
Seoane, Marcos 1 ; Costoya, José A 1   VIAFID ORCID Logo  ; Arce, Víctor M 1 

 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 
Pages
1-7
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2117917819
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.