Krüppel-like factor 4 regulates genetic stability in mouse embryonic fibroblasts

Molecular Cancer

Research

Engda G Hagos¹  Enas A El-Karim²  Amr M Ghaleb²  Vincent W Yang²  Bing Yu² 

[1] Department of Biology, Colgate University, 13346, Hamilton, NY, USA;Department of Medicine, HSC T-16, Rm 020, Stony Brook University, 11794, Stony Brook, NY, USA;

关键词: KLF4;    Genetic instability;    DNA damage responses;    Aneuploidy;    Centrosome amplification;    Mouse embryonic fibroblasts;   

DOI  :  10.1186/1476-4598-12-89

 received in 2013-04-16, accepted in 2013-07-03,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundKrüppel-like factor 4 (KLF4) is a member of the KLF family of transcription factors and regulates proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers including colorectal cancer. We previously showed that KLF4 inhibits cell cycle progression following DNA damage and that mouse embryonic fibroblasts (MEFs) null for Klf4 are genetically unstable, as evidenced by increased rates of cell proliferation, and the presence of DNA double strand breaks (DSBs), centrosome amplification, chromosome aberrations and aneuploidy.MethodsTo determine whether re-expression of Klf4 corrects the observed genetic instability in MEFs null for Klf4 (Klf4−/−), we transfected Klf4−/−MEFs with Klf4-expressing plasmids and compared the results to wild type (Klf4+/+) and untransfected or mock-transfected Klf4−/−MEFs.ResultsWe show that overexpression of Klf4 in Klf4−/−MEFs reduced cell proliferation rates and the proportion of cells with DSBs, abnormal centrosome numbers, aneuploidy and micronuclei. In addition, Klf4-transfected Klf4−/−MEFs exhibited a more robust DNA damage repair response as demonstrated by the greater rate in disappearance of γ-H2AX and 53BP1 foci following γ-irradiation.ConclusionTaken together these findings provide evidence that KLF4 plays a crucial role in the maintenance of genetic stability by modulating the DNA damage response and repair processes.

【 授权许可】

Unknown   
© El-Karim et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.