Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer

Yahata, Hideaki; Kobayashi, Hiroaki; Kamura, Toshiharu; Amada, Satoshi; Hirakawa, Tsubasa; Kohno, Kimitoshi; Kuwano, Michihiko; Nakano, Hitoo

doi:10.1007/s00432-002-0386-6

Cited by 77 publications

(63 citation statements)

References 8 publications

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“…Our observations in clinical samples support the hypothesis that nuclear translocation of YB-1 is involved in the up-regulation of P-glycoprotein in breast cancers, both in those untreated and treated with anticancer drugs. In ovarian cancer, alteration of negative nuclear YB-1 expression in primary lesions to positive nuclear YB-1 expression in recurrent lesions was detected in f30% of tumors treated with regimens containing cisplatin, suggesting that nuclear YB-1 plays an important role in acquired cisplatin resistance in ovarian cancer (22). In the present study, the patients with breast cancer that showed translocation of YB-1 from the cytoplasm to the nucleus showed a significantly reduced response to paclitaxel.…”

Section: Discussionsupporting

confidence: 44%

Increased Nuclear Localization of Transcription Factor Y-Box Binding Protein 1 Accompanied by Up-Regulation of P-glycoprotein in Breast Cancer Pretreated with Paclitaxel

Fujita

Ito²,

Izumi³

et al. 2005

Clinical Cancer Research

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Purpose: The Y-box binding protein 1 (YB-1) regulates expression of P-glycoprotein encoded by the MDR1 gene. There have been no previous studies regarding the involvement of YB-1 in the development of resistance to paclitaxel. The present study was done to examine how paclitaxel affects the localization and expression of YB-1 in breast cancer. Experimental Design: We evaluated the expression and localization of YB-1 and P-glycoprotein in breast cancer tissues obtained from 27 patients before and after treatment with paclitaxel. The effect of paclitaxel on localization of cellular YB-1 was examined by using GFP-YB-1. Interaction of YB-1 with the Y-box motif of the MDR1 promoters was studied by electrophoretic mobility shift assay. The effects of paclitaxel on MDR1 promoter activity were examined by luciferase assay. Results: Of 27 breast cancer tissues treated with paclitaxel, nine (33%) showed translocation of YB-1 from the cytoplasm to the nucleus together with increased expression of P-glycoprotein during the course of treatment. Twelve breast cancer tissues (44%) showed neither translocation of YB-1 nor increased expression of P-glycoprotein. Nuclear translocation of YB-1 was correlated significantly with increased expression of P-glycoprotein (P = 0.0037). Confocal analysis indicated that paclitaxel induced nuclear translocation of green fluorescent fused YB-1 in MCF7 cells. Furthermore, binding of YB-1 to the Y-box of MDR1 promoter was increased in response to treatment with paclitaxel. In addition, MDR1 promoter activity was significantly up-regulated by paclitaxel in MCF7 cells (P < 0.001). Conclusions:The results of the present study suggested that YB-1 may be involved in the development of resistance to paclitaxel in breast cancer.

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Section: Discussionsupporting

confidence: 44%

Increased Nuclear Localization of Transcription Factor Y-Box Binding Protein 1 Accompanied by Up-Regulation of P-glycoprotein in Breast Cancer Pretreated with Paclitaxel

Fujita

Ito²,

Izumi³

et al. 2005

Clinical Cancer Research

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“…In other tumors like ovarian, breast, colon and lung cancers it has been described that YB-1 is frequently overexpressed and shows increased nuclear localization. 29,[31][32][33][34] Nuclear localization of YB-1 correlates with tumor progression and a poor prognosis in tumor patients. 31,32,34 Furthermore, translocation of YB-1 to the nucleus can be achieved by UV irradiation, anticancer agents, hyperthermia, phosphorylation, or association with p53 or splicing factor SRp30c.…”

Section: Discussionmentioning

confidence: 99%

“…29,[31][32][33][34] Nuclear localization of YB-1 correlates with tumor progression and a poor prognosis in tumor patients. 31,32,34 Furthermore, translocation of YB-1 to the nucleus can be achieved by UV irradiation, anticancer agents, hyperthermia, phosphorylation, or association with p53 or splicing factor SRp30c. 13,35,36 The nuclear translocation of YB-1 seen in tumor cells might indicate that the function as a transcriptional regulator preponderates the function as a cytoplasmic mRNA-binding protein.…”

Section: Discussionmentioning

confidence: 99%

“…29,33,34,41 Predominant nuclear localization of YB-1 is characteristic of transformed cells and is also associated with development of multiple drug resistance of cancer cells and the expression of the MDR-1 gene. 29,33,34,42 Targeted disruption of 1 allele of YB-1 in mouse embryonic stem cells increased sensitivity to cisplatin and mitomycin C, but not to etoposide, X-ray or UV irradiation. 43 Transfection of human epidermoid cancer cells with a YB-1 antisense construct resulted in increased sensitivity to cisplatin, mitomycin and UV radiation, suggesting a protective effect of YB-1 against cytotoxic effects of agents that induce crosslinking of DNA.…”

Section: Discussionmentioning

confidence: 99%

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The increased expression of Y box‐binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance

Schittek

Psenner

Sauer

et al. 2007

Intl Journal of Cancer

112

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In previous studies we identified the transcription/translation factor Y-box-binding protein (YB-1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB-1 expression correlates with melanoma progression in vitro and in vivo, we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB-1 expression is increased in melanoma cells in vitro and in vivo and that YB-1 is translocated into the nucleus in invasive and metastatic melanoma cells. To reveal the functional role of YB-1 in melanoma progression we achieved a stable downregulation of YB-1 using shRNA in metastatic melanoma cells. Interestingly, YB-1 downregulation resulted in a pronounced reduced rate of proliferation and an increased rate of apoptotic cell death. In addition, migration and invasion of melanoma cells in monolayer and in a three-dimensional skin reconstruct in vitro was significantly reduced. These effects were accompanied by downregulation of genes involved in proliferation, survival and migration/invasion of melanoma cells such as MMP-2, bcl-2, Cyclin D1, p53 and p16INK4A. Furthermore, melanoma cells with a reduced YB-1 expression showed a decreased resistance to the chemotherapeutic agents cisplatin and etoposide. These data suggest that YB-1 is involved in malignant transformation of melanocytes and contributes to the stimulation of proliferation, tumor invasion, survival and chemoresistance. Thus, YB-1 may be a promising molecular target in melanoma therapy. ' 2007 Wiley-Liss, Inc.

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“…When human cancer cells are treated with ultraviolet (UV) irradiation or anticancer agents, YB-1 translocates into the nucleus [10]. For ovarian cancer it has been shown that nuclear expression of YB-1 is associated with an acquired cisplatin resistance [11]. Transfection of human epidermoid cancer cells with a YB-1-antisense construct resulted in increased sensitivity to cisplatin, mitomycin C and UV radiation, which suggests a protective effect of YB-1 against cytotoxic effects of agents that induce cross-linking of deoxyribonucleic acid (DNA) [12].…”

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confidence: 99%

Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer

Geßner¹,

Woischwill²,

Schumacher³

et al. 2004

European Respiratory Journal

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The human Y-box binding protein, YB-1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB-1 has been associated with chemoresistance and poor prognosis of tumour patients.Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB-1 and p53, in order to evaluate the prognostic role of nuclear expression of YB-1.Cytoplasmic YB-1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB-1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB-1. Patients with nuclear YB-1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB-1 and wildtype p53 (median survival 15 months).This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y-box binding protien seems to be an independent prognostic marker.

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Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer

Cited by 77 publications

References 8 publications

Increased Nuclear Localization of Transcription Factor Y-Box Binding Protein 1 Accompanied by Up-Regulation of P-glycoprotein in Breast Cancer Pretreated with Paclitaxel

Increased Nuclear Localization of Transcription Factor Y-Box Binding Protein 1 Accompanied by Up-Regulation of P-glycoprotein in Breast Cancer Pretreated with Paclitaxel

The increased expression of Y box‐binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance

Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer

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