Open AccessTargeted 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
Author(s) -
Shibahara Kotaro,
Uchiumi Takeshi,
Fukuda Takao,
Kura Shinobu,
Tominaga Yohei,
Maehara Yoshihiko,
Kohno Kimitoshi,
Nakabeppu Yusaku,
Tsuzuki Teruhisa,
Kuwano Michihiko
Publication year - 2004
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2004.tb03214.x
Subject(s) - microbiology and biotechnology , mitomycin c , cisplatin , biology , embryonic stem cell , cytotoxic t cell , western blot , gene , in vitro , genetics , chemotherapy
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.