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

• Published in: Cancer science Vol. 95; no. 4; pp. 348 - 353
• Main Authors: Shibahara, Kotaro, Uchiumi, Takeshi, Fukuda, Takao, Kura, Shinobu, Tominaga, Yohei, Maehara, Yoshihiko, Kohno, Kimitoshi, Nakabeppu, Yusaku, Tsuzuki, Teruhisa, Kuwano, Michihiko
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2004; Blackwell; John Wiley & Sons, Inc
• Subjects: Alleles; Animals; Antineoplastic Agents, Alkylating - pharmacology; Biological and medical sciences; CCAAT-Enhancer-Binding Proteins - deficiency; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - physiology; Cell proliferation; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Cells, Cultured - radiation effects; Cisplatin; Cisplatin - pharmacology; Colony-Forming Units Assay; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - drug effects; DNA Damage - genetics; DNA Damage - radiation effects; DNA repair; Drug resistance; Drug Resistance, Neoplasm - genetics; Embryo cells; Embryo, Mammalian - cytology; Etoposide; Etoposide - pharmacology; Gene Targeting; Heterozygote; Medical sciences; Mice; Mitomycin - pharmacology; Mitomycin C; NFI Transcription Factors; RNA, Messenger - genetics; Stem cell transplantation; Stem cells; Stem Cells - drug effects; Stem Cells - metabolism; Stem Cells - radiation effects; Transcription; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology; Tumors; Ultraviolet radiation; Ultraviolet Rays; Y-Box-Binding Protein 1; Antineoplastic agent; Mitomycin; Stem cell; Rodentia; Hematopoietic cell; Cisplatin; Binding protein; Alkylating agent; Vertebrata; Allele; Antibiotic; Sensitivity; Mammalia; Cancerology; Gene; Mouse; Embryonic cell; Animal; Genetics; Mutation
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2004.tb03214.x

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.