Human Y-box binding protein1(YB-1) : Mechanism for the nuclear translocation and its role of tumor growth and drug resistance-

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590324
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyushu University (2008); Kurume University (2007)
• Principal Investigator: KUWANO Michihiko Kyushu University, 先端融合医療レドックスナビ研究拠点, 特任教授 (80037431)
• Project Period (FY): 2007 – 2008
• Keywords: YB-1 / YB-1核内局在 / 多剤耐性 / EGF受容体ファミリー / 乳癌 / P-糖蛋白質 / MVP / LRP / エストラジオール受容体

Research Abstract

我々はがん治療後のP-糖蛋白質(ABCB1)依存性多剤耐性がんの発現にY-ボックス結合蛋白-1(YB-1)が深く関与することをはじめて発見した。本研究では、増殖シグナルによるYB-1 の核内移行にP13k/Akt による活性化が必要であり、多くのヒトがん細胞の増殖を制御し、YB-1 の核内局在がヒト卵巣癌、乳癌や軟部腫瘍などにおいて耐性および増殖関連遺伝子の発現や患者の予後と有意に相関することなどを見出した。以上、YB-1 はがん治療の有用なバイオマーカーであると確信している。

Research Products

• [Journal Article] M.N-myc downstream regulated gene 1/Cap43 suppresses tumor growth and angiogenesis of pancreatic cancer through attenuation of IKKbeta expression (2009)
  • Author(s): Hosoi, F., Izumi, H., Kawahara, A., Yuichi, M., Kinoshita, H., Kage, M., Nishio, K., Kohno, K., Kuwano, M., and Ono
  • Journal Title: Cancer Res. 69 Pages: 4983-4991
  • Peer Reviewed
• [Journal Article] Higher expression of deoxyuridinetriphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer (2009)
  • Author(s): Kawahara, A., Akagi, Y., Hattori, S., Mizobe, T., Shirouzu, K., Ono, M., Yanagawa, T., Kuwano, M and Kage, M
  • Journal Title: J.Clinic. Pathology 62 Pages: 364-369
  • Peer Reviewed
• [Journal Article] Overexpression of class III・-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma (2009)
  • Author(s): Aoki, D., Oda, Y., Hattori, S., Taguchi, K., Ohishi, Y., Basaki, Y., Oie, S., Suzuki, N., Kono, S., Tsuneyoshi, M., Ono, M., Kuwano, M
  • Journal Title: Clinic.Cancer Res. 15 Pages: 1473-1480
  • Peer Reviewed
• [Journal Article] Role of macrophages in inflammatory . lymphangiogenesis : Enhanced production of vascular endothelial growth factor C and Dthrough NF-κB activation (2008)
  • Author(s): Watari, K., Nakao, S., Fotovati, A., Basaki, Y., Hosoi, F., Bereczky, B., Higuchi, R. Miyamoto, T., Kuwano, M., and Ono
  • Journal Title: Biochem. Biophys. Res. Commun. 377 Pages: 826-831
  • Peer Reviewed
• [Journal Article] Growth inhibitory effects of pegylated IFN-alpha2b and5-fluorouracil in combination on renal cell carcinoma cell lines in vitro and in vivo (2008)
  • Author(s): Moriya, F., Ogasawara, S., Basaki, Y., Akiba, J., Kojiro, S., Fukahori, S., Ishizaki, H., Nishida, N., Matsuoka, K., Kojiro, M., Kuwano, M., and Yano, H
  • Journal Title: Int. J. Oncol. 33 Pages: 647-655
  • Peer Reviewed
• [Journal Article] Molecular basis for the induction of an angiogenesis inhibitor thrombospondin-1, by 5-fluorouracil (2008)
  • Author(s): Zhao, H., Ooyama, A., Yamamoto, M., Ikeda, R., Haraguchi, M., Tabata, S., Furukawa, T., Che, X., Zhang, S., Oka, T., Fukushima, M., Nakagawa, M., Ono, M., Kuwano, M., and Akiyama, S
  • Journal Title: Cancer Res. 68 Pages: 7035-7041
  • Peer Reviewed
• [Journal Article] Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in human colon cancer KM12C cells (2008)
  • Author(s): Zhao, H., Ooyama, A., Yamamoto, M., Ikeda, R., Haraguchi, M., Tabata, S., Furukawa, T., Che, X., Iwashita, K., Oka, T., Fukushima, M., Nakagawa, M., Ono, M., Kuwano, M., and Akiyama, S
  • Journal Title: Cancer Lett. 270 Pages: 156-163
  • Peer Reviewed
• [Journal Article] Inhibition of bone and muscle metastases of lung cancer cells by decrease in the number of monocytes/macrophages (2008)
  • Author(s): Hiraoka, K., Zenmyo, M., Watari, K., Iguchi, H., Fotovati, A., Kimura, Y., Hosoi, F., Shoda, T., Nagata, K., Osada, H., Ono, M., and Kuwano, M
  • Journal Title: Cancer Sci. 99 Pages: 1595-1602
  • Peer Reviewed
• [Journal Article] Different expression profiles of Y-box-binding protein-1 and multidrug resistance-associated proteins between alveolar and embryonal rhabdomyosarcoma (2008)
  • Author(s): Oda, Y., Kohashi, K., Yamamoto, H., Tamiya, S., Kohno, K., Kuwano, M., Iwamoto, Y., Tajiri, T., Taguchi, T., and Tsuneyoshi, M
  • Journal Title: Cancer Sci. 99 Pages: 726-732
  • Peer Reviewed
• [Journal Article] Preclinical and clinical studies of novel breast cancer drugs targeting molecules involved in protein kinase C signaling, the putative metastasis-suppressor gene Cap43 and the Y-box binding protein-1 (2008)
  • Author(s): Fujii, T., Yokoyama, G., Takahashi, H., Toh, U., Kage, M., Ono, M., Shirouzu, K., and Kuwano, M
  • Journal Title: Current Medicinal Chem. 15 Pages: 528-537
  • Peer Reviewed
• [Journal Article] Preclinical studies of molecular-targeting diagnostic and therapeutic strategies against breast cancer (2008)
  • Author(s): Fujii, T., Yokoyama, G., Takahashi, H., Namoto, R., Nakagawa, S., Toh, U., Kage, M., Shirouzu, K., and Kuwano, M
  • Journal Title: Breast Cancer 15 Pages: 73-78
  • Peer Reviewed
• [Journal Article] Ets Transcription factors regulate peroxiredoxin1 and peroxiredoxin5 expression through their interaction with the high mobility group protein HMGB1 (2008)
  • Author(s): Shiota, M., Izumi, H., Miyamoto, N., Onitsuka, T., Kashiwagi, E., Kidani, A., Hirano, G., Ono, M., Kuwano, M., Naito, S., Sasaguri, Y., and Kohno, K
  • Journal Title: Cancer Sci. 99 Pages: 1950-1959
  • Peer Reviewed
• [Journal Article] Cap43/NDRG1/Drg-1 is a molecular target for angiogenesis and a prognostic indicator in cervical adenocarcinoma (2008)
  • Author(s): Nishio, S., Tsuda, N., Takemoto, S., Kawano, K., Ushijima, K., Yamaguchi, T., Nishida, N., Kakuma, T., Tsuda, H., Kasamatsu, T., Sasajima, Y., Kage, M., Kuwano, M., and Kamura , T
  • Journal Title: Cancer Lett. 264 Pages: 36-43
  • Peer Reviewed
• [Journal Article] Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice (2008)
  • Author(s): Koga, M., Kai,H., Egami, K., Murohara, T., Ikeda, A., Yasuoka, S.,Egashira, K., Matsuishi, T., Kai, M., Kataoka, Y., Kuwano, M., and Imaizumi, T
  • Journal Title: Biochem. Biophys. Res. Commun. 365 Pages: 279-284
  • Peer Reviewed
• [Journal Article] Expression of HER2 and estrogen receptor alpha depends upon nuclear localization of Y-box binding protein-1 in human breast cancers (2008)
  • Author(s): Fujii, T., Kawahara, A., Basaki, Y., Hattori, S., Nakashima, K., Nakano, K., Shirouzu, K., Kohno, K., Yanagawa, T., Yamana, H., Nishio, K., Ono, M., Kuwano, M., and Kage, M
  • Journal Title: Cancer Res. 68 Pages: 1504-1512
  • Peer Reviewed
• [Journal Article] Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis (2007)
  • Author(s): Kimura, Y., Watari, K., Fotovati, A., Hosoi, F., Yasumoto, K., Izumi, H., Kohno, K., Umezawa, K., Iguchi, H., Shirouzu, K., Takamori, S., Kuwano, M.,and Ono,M
  • Journal Title: Cancer Sci. 98 Pages: 2009-2018
  • Peer Reviewed
• [Journal Article] Expression profile of class I histone deacetylases in human cancer tissues (2007)
  • Author(s): Nakagawa, M., Oda, Y., Eguchi, T., Aishima, S., Yao, T., Hosoi, F., Basaki, Y., Ono, M., Kuwano, M., Tanaka, M., and Tsuneyoshi, M
  • Journal Title: Oncology Rep. 18 Pages: 769-774
  • Peer Reviewed
• [Journal Article] Immunohistochemical expression of Cap43 and Mina53 proteins in neuroblastoma (2007)
  • Author(s): Fukahori, S., Yano, H., Tsuneoka, M., Tanaka, Y., Yagi, M., Kuwano, M., Tajiri, T., Taguchi, T., Tsuneyoshi, M., and Kojiro, M
  • Journal Title: J Pediatric Surgery 42 Pages: 1831-1840
  • Peer Reviewed
• [Journal Article] Dexamethasone inhibits IL-1b-induced corneal neovascularization : role of NF-kB-activated stromal cells in inflammatory angiogenesis (2007)
  • Author(s): Nakao, S., Hata, Y., Miura, M., Noda, K., Kimura, Y., Kawahara, S., Kita, T., Hisatomi, T., Nakazawa, T., Jin, Y., Dana, R., Kuwano, M., Ono, M., Ishibashi, T. and Hafezi-Moghadam, A
  • Journal Title: Am. J. Path. 171 Pages: 1058-1065
  • Peer Reviewed
• [Journal Article] Alteration of dihydropyrimidine dehydrogenase expression by interferon-・ affects the antiproliferative effects of 5-fluorouracil in human hepatocellular carcinoma cells (2007)
  • Author(s): Oie, S., Ono M., Fukushima, H., Hosoi, F., Yano, H., Maruyama Y., Kojiro, M., Terada, T., Hirano K., Kuwano M., and Yamada, Y
  • Journal Title: Molec. Cancer Therapeut. 6 Pages: 2310-2318
  • Peer Reviewed
• [Journal Article] Expression of beta-tubulin isotypes in human primary ovarian carcinoma (2007)
  • Author(s): Ohishi, Y., Oda, Y., Basaki, Y., Kobayashi, H., Wake, N., Kuwano, M.,c and Tsuneyoshi, M
  • Journal Title: Gynecol. Oncol 105 Pages: 586-592
  • Peer Reviewed
• [Journal Article] Prognostic inmlication of nuclear localization of the Y-box-binding protein-1 and CXC4 expression in ovarian cancer : Their correlation with activated Akt, LRP/MVP and P-glycoprotein expression (2007)
  • Author(s): Oda, Y., Ohishi, Y., Basaki, Y., Kobayashi, H., Hirakawa, T., Wake, N., Ono, M, Nishio, K, Kuwano, M
  • Journal Title: Cancer Sci. 98 Pages: 1020-1026
  • Peer Reviewed
• [Journal Article] Akt-dependent nuclear localisation of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells (2007)
  • Author(s): Basaki, Y., Hosoi, F., Oda, Y., Fotovati, A., Maruyama, Y., Oie, S., Ono, M., Izumi, H., Kohno, K.,Shimoyama, T., Nishio, K., and Kuwano M
  • Journal Title: Oncogene 26 Pages: 2736-2746
  • Peer Reviewed
• [Presentation] 血管新生抑制剤 : その歴史と将来 (2009)
  • Author(s): 桑野信彦
  • Organizer: 第7回日本臨床腫瘍学会学術集会
  • Place of Presentation: 名古屋(教育講演)
  • Year and Date: 2009-03-21
• [Presentation] 血管新生を標的としたがん治療の展開 (2009)
  • Author(s): 桑野信彦
  • Organizer: 中国・四国広域がんプロ養成コンソーシアム
  • Place of Presentation: 徳島
  • Year and Date: 2009-02-13
• [Presentation] がん治療の最前線と新しい時代 (2008)
  • Author(s): 桑野信彦
  • Organizer: 第11回メディカルサミット2008
  • Place of Presentation: 福岡
  • Year and Date: 2008-09-21
• [Presentation] がんのレドックス応答と発症から進展を標的とした診断・創薬のイノベーション研究 (2008)
  • Author(s): 桑野信彦
  • Organizer: 第7回国際バイオフォーラム
  • Place of Presentation: 東京
  • Year and Date: 2008-07-02
• [Presentation] がんのバイオマーカーとしてのY-ボックス結合蛋白-1(YB-1)の核内局在 (2008)
  • Author(s): 桑野信彦
  • Organizer: 第12回分子標的がん治療研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-26
• [Presentation] がん化学療法のあり方"-基礎医学の立場から(合同シンポジウム) (2007)
  • Author(s): 桑野信彦
  • Organizer: 日本癌治療学会総会
  • Place of Presentation: 京都
  • Year and Date: 20071024-26
• [Presentation] 抗癌剤の感受性・耐性の分子機序と癌最適化医療(特別講演) (2007)
  • Author(s): 桑野信彦
  • Organizer: 第46回日本臨床細胞学会秋季大会
  • Place of Presentation: 宮城
  • Year and Date: 2007-12-01
• [Patent(Industrial Property Rights)] EGFレセプターを標的とした薬剤の有効性の予測方法 (2009)
  • Inventor(s): 桑野信彦
  • Industrial Property Rights Holder: 国立大学法人九州大学
  • Industrial Property Number: 米国仮出願
  • Filing Date: 2009-01-26
  • Overseas