Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer.
OBJECTIVE
Nuclear expression of Y box-binding protein (YB-1), a member of the DNA-binding protein family, was recently reported to have a much higher concentration in cisplatin-resistant cancer cell lines than in their drug-sensitive parental counterparts, suggesting the ability to induce cisplatin resistance. Ovarian cancer has been generally treated with cisplatin-based chemotherapy and often recurs due to acquired cisplatin resistance. The aim of our study is to elucidate the association between nuclear YB-1 and cisplatin resistance in human ovarian cancer using cultured cell lines and surgical specimens.


METHODS
Intracellular YB-1 localization was examined by Western blot analysis for both cisplatin sensitive and resistant human ovarian cancer cell lines. Moreover, 35 pairs of surgical specimens derived from primary and matched recurrent ovarian cancers of the same patient were evaluated for their nuclear YB-1 expression by immunohistochemical staining.


RESULTS
Western blot analysis for nuclear and cytoplasmic extracts indicated that cisplatin-resistant cells showed much higher nuclear YB-1 expression than sensitive parental cells. Immunohistochemical analysis showed that ten paired cases turned from negative nuclear YB-1 in primary lesions to positive nuclear YB-1 in recurrent lesions, whereas only two paired cases showed a reverse turn from positive to negative.


CONCLUSIONS
The expression of YB-1 in the nucleus seems to be associated with acquired cisplatin resistance in ovarian cancers. Nuclear YB-1 might be a useful predictive marker indicating cisplatin sensitivity and/or a target molecule to treat recurring ovarian cancers by cisplatin-based second-line chemotherapy.
Yahata
Hideaki
H
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Kobayashi
Hiroaki
H
Kamura
Toshiharu
T
Amada
Satoshi
S
Hirakawa
Toshio
T
Kohno
Kimitoshi
K
Kuwano
Michihiko
M
Nakano
Hitoo
H
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use*; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D051840:Y-Box-Binding Protein 1
D000970:Antineoplastic Agents; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D002945:Cisplatin