Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells

Y. Basaki, F. Hosoi, Yoshinao Oda, A. Fotovati, Y. Maruyama, S. Oie, M. Ono, H. Izumi, K. Kohno, K. Sakai, T. Shimoyama, K. Nishio, M. Kuwano

研究成果: ジャーナルへの寄稿記事

87 引用 (Scopus)

抄録

Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.

元の言語英語
ページ(範囲)2736-2746
ページ数11
ジャーナルOncogene
26
発行部数19
DOI
出版物ステータス出版済み - 4 26 2007

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Y-Box-Binding Protein 1
Ovarian Neoplasms
Small Interfering RNA
Genes
Down-Regulation
Cyclin B
Thymidylate Synthase
Calcium-Binding Proteins
DNA-Binding Proteins
Multiple Drug Resistance
Type C Phospholipases
Cadherins
Oligonucleotide Array Sequence Analysis
Drug Resistance
Heterografts
Shock
Neoplasms
Cytoplasm
Animal Models
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

これを引用

Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells. / Basaki, Y.; Hosoi, F.; Oda, Yoshinao; Fotovati, A.; Maruyama, Y.; Oie, S.; Ono, M.; Izumi, H.; Kohno, K.; Sakai, K.; Shimoyama, T.; Nishio, K.; Kuwano, M.

:: Oncogene, 巻 26, 番号 19, 26.04.2007, p. 2736-2746.

研究成果: ジャーナルへの寄稿記事

Basaki, Y, Hosoi, F, Oda, Y, Fotovati, A, Maruyama, Y, Oie, S, Ono, M, Izumi, H, Kohno, K, Sakai, K, Shimoyama, T, Nishio, K & Kuwano, M 2007, 'Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells', Oncogene, 巻. 26, 番号 19, pp. 2736-2746. https://doi.org/10.1038/sj.onc.1210084
Basaki, Y. ; Hosoi, F. ; Oda, Yoshinao ; Fotovati, A. ; Maruyama, Y. ; Oie, S. ; Ono, M. ; Izumi, H. ; Kohno, K. ; Sakai, K. ; Shimoyama, T. ; Nishio, K. ; Kuwano, M. / Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells. :: Oncogene. 2007 ; 巻 26, 番号 19. pp. 2736-2746.
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abstract = "Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.",
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T1 - Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells

AU - Basaki, Y.

AU - Hosoi, F.

AU - Oda, Yoshinao

AU - Fotovati, A.

AU - Maruyama, Y.

AU - Oie, S.

AU - Ono, M.

AU - Izumi, H.

AU - Kohno, K.

AU - Sakai, K.

AU - Shimoyama, T.

AU - Nishio, K.

AU - Kuwano, M.

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N2 - Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.

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