• Open Access

Targeted disruption of one allele of the Y-box binding protein-1 (YB-1) gene in mouse embryonic stem cells and increased sensitivity to cisplatin and mitomycin C

Authors


To whom correspondence should be addressed. E-mail: uchiumi@biochem1.med.kyushu-u.ac.jp

Abstract

The eukaryotic Y-box binding protein-1 (YB-1) functions in various biological processes, including transcriptional and translational control, DNA repair, drug resistance, and cell proliferation. To elucidate the physiological role of the YB-1 protein, we disrupted one allele of mouse YB-1 in embryonic stem (ES) cells. Northern blot analysis revealed that YB-1+/- ES cells with one intact allele contain approximately one-half the amount of mRNA detected in wild-type (YB-1+/+) cells. We further found that the protein level of YB-1+/- cells was reduced to approximately 50–60% compared with that of YB-1+/+ cells. However, no apparent growth difference was found between YB-1+/- and YB-1+/+ cells. YB-1+/- cells showed increased sensitivity to cisplatin and mitomycin C, but not to etoposide, X-ray or UV irradiation, as compared to YB-1+/+ cells. YB-1 may have the capacity to exert a protective role against cytotoxic effects of DNA damaging agents, and may be involved in certain aspects of drug resistance.

Abbreviations:
YB-1

Y-box binding protein-1

ES

embryonic stem

MTS

[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt

PES

phenazine ethosulfate

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