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Molecular Cancer
Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Research

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

Authors: Enas A El-Karim, Engda G Hagos, Amr M Ghaleb, Bing Yu, Vincent W Yang

Published in: Molecular Cancer | Issue 1/2013

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Abstract

Background

Krüppel-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.

Methods

To 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.

Results

We 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.

Conclusion

Taken 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.
Appendix
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Metadata
Title
Krüppel-like factor 4 regulates genetic stability in mouse embryonic fibroblasts
Authors
Enas A El-Karim
Engda G Hagos
Amr M Ghaleb
Bing Yu
Vincent W Yang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-89

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