Analysis of vitamin K target gene network mediated by nuclear receptors and post-translational protein modification

• Project/Area Number: 19591084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Saitama Medical University
• Principal Investigator: HORIE Kuniko Saitama Medical University, 医学部, 准教授 (90261982)
• Co-Investigator(Kenkyū-buntansha): INOUE Satoshi 埼玉医科大学, 医学部, 客員教授 (40251251)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ビタミンK / 核内受容体 / 翻訳後蛋白修飾 / 骨芽細胞 / 遺伝子発現調節

Research Abstract

骨芽細胞におけるビタミンK 作用として、メナキノン-4 特異的なプロテインキナーゼA のリン酸化修飾による新しい作用経路を発見した。クロマチン免疫沈降を用いたゲノムタイリングアレイによるステロイド受容体結合部位のデータを活用し、骨芽細胞系におけるステロイド標的遺伝子を同定する手法を確立した。当グループが明らかにした骨におけるビタミンK 作用点である核内受容体SXR については、本研究により骨代謝における調節因子としての重要性が示唆された。

Research Products

• [Journal Article] Modulation of adipogenesis-related gene expression by estrogen-related receptor gamma during adipocytic differentiation. (2009)
  • Author(s): Kubo M, Ijichi N, Ikeda K, Horie-Inoue K, Takeda S, Inoue S.
  • Journal Title: Biochim Biophys Acta 1789 Pages: 71-77
  • Peer Reviewed
• [Journal Article] Identification of Igf2, Igfbp2 and Enpp2 as estrogen-responsive genes in rat hippocampus. (2009)
  • Author(s): Takeo C, Ikeda K, Horie-Inoue K, Inoue S.
  • Journal Title: Endocr J 56 Pages: 113-120
  • Peer Reviewed
• [Journal Article] EBAG9 is a tumor-promoting and prognostic factor for bladder cancer. (2009)
  • Author(s): Kumagai J, Urano T, Ogushi T, Takahashi S, Horie-Inoue K, Fujimura T, Azuma K, Muramatsu M, Ouchi Y, Kitamura T, Inoue S.
  • Journal Title: Int J Cancer 124 Pages: 799-805
  • Peer Reviewed
• [Journal Article] Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth. (2009)
  • Author(s): Takayama K, Tsutsumi S, Suzuki T, Horie-Inoue K, Ikeda K, Kaneshiro K, Fujimura T, Kumagai J, Urano T, Sakaki Y, Shirahige K, Sasano H, Takahashi S, Kitamura T, Ouchi Y, Aburatani H, Inoue S.
  • Journal Title: Cancer Res. 69 Pages: 137-142
  • Peer Reviewed
• [Journal Article] Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth (2009)
  • Author(s): Takayama K
  • Journal Title: Cancer Res 69 Pages: 137-142
  • Peer Reviewed
• [Journal Article] Modulation of adipogenesis-related gene expression by estrogen-related receptor gamma during adipocytic differentiation (2009)
  • Author(s): Kubo M
  • Journal Title: Biochim Biophys Acta 1789 Pages: 71-77
  • Peer Reviewed
• [Journal Article] EBAG9 is a tumor-promoting and prognostic factor for bladder cancer (2009)
  • Author(s): Kumagai J
  • Journal Title: Int J Cancer 124 Pages: 799-805
  • Peer Reviewed
• [Journal Article] Identification of Igf2, Igfbp2 and Enpp2 as estrogen-responsive genes in rat hippocampus (2009)
  • Author(s): Takeo C
  • Journal Title: Endocr J 56 Pages: 113-120
  • Peer Reviewed
• [Journal Article] FOXP1 is an androgen-responsive transcription factor that negatively regulates androgen receptor signaling in prostate cancer cells. (2008)
  • Author(s): Takayama K, Horie-Inoue K, Ikeda K, Urano T, Murakami K, Hayashizaki Y, Ouchi Y, Inoue S.
  • Journal Title: Biochem Biophys Res Commun 374 Pages: 388-393
  • Peer Reviewed
• [Journal Article] FOXPI is an androgen-responsive transcription factor that negatively regulates androgen receptor signaling in prostate cancer cells (2008)
  • Author(s): Takayama K
  • Journal Title: Biochem Biophys Res Commun 374 Pages: 388-393
  • Peer Reviewed
• [Journal Article] Steroid and xenobiotic receptor mediates a novel vitamin K2 signaling pathway in osteoblastic cells. (2007)
  • Author(s): Horie-Inoue K, Inoue S.
  • Journal Title: J Bone Miner Metab 26 Pages: 9-12
  • Peer Reviewed
• [Journal Article] Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells. (2007)
  • Author(s): Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S.
  • Journal Title: J Mol Endocrinol 39 Pages: 239-247
  • Peer Reviewed
• [Journal Article] Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis. (2007)
  • Author(s): Takayama K, Kaneshiro K, Tsutsumi S, Horie-Inoue K, Ikeda K, Urano T, Ijichi N, Ouchi Y, Shirahige K, Aburatani H, Inoue S.
  • Journal Title: Oncogene 26 Pages: 4453-4463
  • Peer Reviewed
• [Journal Article] Increased expression of estrogen-related receptor alpha (ERRalpha) is a negative prognostic predictor in human prostate cancer. (2007)
  • Author(s): Fujimura T, Takahashi S, Urano T, Kumagai J, Ogushi T, Horie-Inoue K, Ouchi Y, Kitamura T, Muramatsu M, Inoue S.
  • Journal Title: Int J Cancer. 120 Pages: 2325-2330
  • Peer Reviewed
• [Journal Article] Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer. (2007)
  • Author(s): Kumagai J, Fujimura T, Takahashi S, Urano T, Ogushi T, Horie-Inoue K, Ouchi Y, Kitamura T, Muramatsu M, Blumberg B, Inoue S.
  • Journal Title: Prostate 67 Pages: 1029-1037
  • Peer Reviewed
• [Journal Article] Estrogen-related receptor alpha modulates the expression of adipogenesis-related genes during adipocyte differentiation. (2007)
  • Author(s): Ijichi N, Ikeda K, Horie-Inoue K, Yagi K, Okazaki Y, Inoue S.
  • Journal Title: Biochem Biophys Res Commun 358 Pages: 813-818
  • Peer Reviewed
• [Journal Article] Association of the HTRA1 gene variant with age-related macular degeneration in the Japanese population. (2007)
  • Author(s): Mori K, Horie-Inoue K, Kohda M, Kawasaki I, Gehlbach PL, Awata T, Yoneya S, Okazaki Y, Inoue S.
  • Journal Title: J Hum Genet 52 Pages: 636-641
  • Peer Reviewed
• [Journal Article] Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells (2007)
  • Author(s): Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S
  • Journal Title: J Mol Endocrinol 39 Pages: 239-247
  • Peer Reviewed
• [Journal Article] Steroid and xenobiotic receptor mediates a novel vitamin K2 signaling pathway in osteoblastic cells (2007)
  • Author(s): Horie-Inoue K, Inoue S
  • Journal Title: J Bone Miner Metab 26 Pages: 9-12
  • Peer Reviewed
• [Journal Article] Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis (2007)
  • Author(s): Takayama K, Horie-Inoue K, Aburatani H, Inoue S, (他7名)
  • Journal Title: Oncogene 26 Pages: 4453-4463
  • Peer Reviewed
• [Presentation] 核内受容体PXR ノックアウトマウスは著明な骨量減少を呈する (2009)
  • Author(s): 東浩太郎、Stephanie Casey、浦野友彦、堀江公仁子、大内尉義、Bruce Blumberg、井上聡.
  • Organizer: 第12 回Vitamin K & Aging 研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-14
• [Presentation] 核内受容体PXRノックアウトマウスは著明な骨量減少を呈する (2009)
  • Author(s): 東 浩太郎
  • Organizer: 第12回Vitamin K & Aging研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-14
• [Presentation] 核内受容体PXR ノックアウトマウスは海綿骨および皮質骨の骨量減少を呈する (2008)
  • Author(s): 東浩太郎、Stephanie Casey、浦野友彦、堀江公仁子、大内尉義、Bruce Blumberg、井上聡.
  • Organizer: 第26 回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-10-29
• [Presentation] 核内受容体PXRノックアウトマウスは海綿骨および皮質骨の骨量減少を呈する (2008)
  • Author(s): 東 浩太郎
  • Organizer: 第26回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-10-29
• [Presentation] Systemic identification of common and unique response genes for various steroid hormones in the human ENCODE genomic regions. (2008)
  • Author(s): Horie-Inoue K, Takayama K, Ikeda K, Inoue S.
  • Organizer: CBI Annual Meeting 2008 International Symposium
  • Place of Presentation: 東京
  • Year and Date: 2008-10-23
• [Presentation] Systemic identification of common and unique response genes for various steroid hormones in the human ENCODE genomic regions (2008)
  • Author(s): Horie K
  • Organizer: CBI Annual Meeting 2008 International Symposium
  • Place of Presentation: 東京
  • Year and Date: 2008-10-23
• [Presentation] Common and differential responses to steroid hormones via their cognate receptor-binding sites in human genome. (2007)
  • Author(s): Horie-Inoue K, Takayama K, Inoue S.
  • Organizer: 21st International Mammalian Genome Conference
  • Place of Presentation: 京都
  • Year and Date: 2007-10-28
• [Presentation] ChIP-on-chip analysis reveals novel glucocorticoid response genes adjacent to genomic binding sites for steroid hormone receptor in osteoblastic cells. (2007)
  • Author(s): Horie-Inoue K, Takayama K, Inoue S.
  • Organizer: 第29 回米国骨ミネラル研究学会年会
  • Place of Presentation: 米国・ホノルル
  • Year and Date: 2007-09-17
• [Presentation] ChIP-on-chip analysis reveals novel glucocorticoid response genes adjacent to genomic binding sites for steroid hormone receptor in osteoblastic cells (2007)
  • Author(s): Horie-Inoue K, Takayama K, Inoue S
  • Organizer: 第29回米国骨ミネラル研究学会年会
  • Place of Presentation: 米国・ホノルルコンベンションセンター
  • Year and Date: 2007-09-17
• [Book] 転写因子による生命現象解明の最前線 第4 章 遺伝情報発現と疾患 6 節:ビタミンK 作用と疾患 -核内受容体を介する発現調節機構への新展開(分担執筆) (2007)
  • Author(s): 堀江公仁子、井上聡(五十嵐和彦、深水昭吉、大熊芳明、山本雅之編)
  • Publisher: 羊土社
• [Book] 転写因子による生命現象解明の最前線 第4章 遺伝情報発現と疾患 6節:ビタミンK作用と疾患-核内受容体を介する発現調節機構への新展開(分担執筆) (2007)
  • Author(s): 堀江 公仁子、井上 聡(五十嵐 和彦、深水 昭吉、大熊 芳明、山本 雅之編)
  • Total Pages: 7
  • Publisher: 羊土社