Elucidation of CD109 function and its tumor promotion using transgenic mice overexpressing CD109

• Project/Area Number: 22790532
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Laboratory medicine
• Research Institution: Chubu University
• Principal Investigator: SOBUE Sayaka 中部大学, 臨床検査技術教育・実習センター, 助教 (50513347)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: CD109 / トランスジェニックマウス / モノクローナル抗体

Research Abstract

In this study, I first generated a transgenic mouse overexpressing CD109 under control of CAG promoter and investigated its molecular function using the transgenic mouse. I observed elevated serum-concentration of soluble form of CD109. Thereafter I found tumor development in one-third of the transgenic mice around the age of one year. Its molecular mechanisms remain under study. I next investigated why CD109 is up-regulated during carcinogenesis in several carcinomas by promoter analysis of CD109. I finally demonstrated that CD109 expression is up-regulated in subsets of carcinomas through Egr1 induction during their carcinogenesis.

Research Products

• [Journal Article] Sphingosine kinase 1 expression is downregulated during differentiation of Friend cells due to decreased c-MYB. (2013)
  • Author(s): Mizutani N, Kobayashi M, Sobue S, Ichihara M, Ito H, Tanaka K, Iwaki S, Fujii S, Ito Y, Tamiya-Koizumi K, Takagi A, Kojima T, Naoe T, Suzuki M, Nakamura M, Banno Y, Nozawa Y, Murate T.
  • Journal Title: Biochim Biophys Acta. Volume: 1833 Pages: 1006-1016
  • Peer Reviewed
• [Journal Article] Epidermal Hyperplasia and AppendageAbnormalities in Mice Lacking CD109. (2012)
  • Author(s): Mii S, Murakumo Y, Asai N, Jijiwa M, Hagiwara S, Kato T, Asai M, Enomoto A, Ushida K, Sobue S, Ichihara M, Takahashi M
  • Journal Title: Am J Pathol. Volume: 181 Pages: 1180-1189
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of neutral sphingomyelinase 2 in all-trans retinoic acid-treated human breast cancer cell line (2012)
  • Author(s): Ito H, Tanaka K, Hagiwara K, Kobayashi M, Hoshikawa A, Mizutani N, Takagi A, Kojima T, Sobue S, Ichihara M, Suzuki M, Tamiya-Koizumi K, Nakamura M, Banno Y, Nozawa Y, Murate T.
  • Journal Title: MCF-7. J Biochem. Volume: 151 Pages: 599-610
  • Peer Reviewed
• [Journal Article] Hasegawa T.Analysis of the pathological lesions of the lung in a mouse model of cutaneousinfection with Streptococcus pyogenes. (2012)
  • Author(s): Minami M, Sobue S, Ichihara M
  • Journal Title: Pathol Int. Volume: 62 Pages: 99-104
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of neutral sphingomyelinase 2 in all-trans retinoic acid-treated human breast cancer cell line, MCF-7. (2012)
  • Author(s): Ito H
  • Journal Title: J Biochem. Volume: 151 Issue: 6 Pages: 599-610
  • DOI: 10.1093/jb/mvs037
  • Peer Reviewed
• [Journal Article] Epidermal Hyperplasia and Appendage Abnormalities in Mice Lacking CD109. (2012)
  • Author(s): Mii S
  • Journal Title: Am J Pathol. Volume: 181 Pages: 1180-1189
  • Peer Reviewed
• [Journal Article] Analysis of the pathological lesions of the lung in a mouse model of cutaneous infection with Streptococcus pyogenes (2012)
  • Author(s): Minami M, Sobue S, Ichihara M, Hasegawa T
  • Journal Title: Pathol Int Volume: 62 Issue: 2 Pages: 99-104
  • DOI: 10.1111/j.1440-1827.2011.02756.x
  • NAID: 10031185174
  • Peer Reviewed
• [Journal Article] Sphingosine Kinase 1/S1P PathwayInvolvement in the GDNF-Induced GAP43Transcription. (2011)
  • Author(s): Murakami M, Ito H, Hagiwara K, Kobayashi M, Hoshikawa A, Takagi A, Kojima T, Tamiya-Koizumi K, Sobue S, Ichihara M, Suzuki M, Banno Y, Nozawa Y, Murate T.
  • Journal Title: J Cell Biochem. Volume: 112 Pages: 3449-3458
  • Peer Reviewed
• [Journal Article] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines. (2011)
  • Author(s): Ito H, Yoshida K, Murakami M, Hagiwara K, Sasaki N, Kobayashi M, Takagi A, Kojima T, Sobue S, Suzuki M, Tamiya-Koizumi K, Nakamura M, Banno Y, Nozawa Y, Murate T.
  • Journal Title: Biochim Biophys Acta. Volume: 1811 Pages: 119-128
  • Peer Reviewed
• [Journal Article] Sphingosine Kinase 1/S1P Pathway Involvement in the GDNF-Induced GAP43 Transcription (2011)
  • Author(s): Murakami M
  • Journal Title: J Cell Biochem Volume: 112 Issue: 11 Pages: 3449-3458
  • DOI: 10.1002/jcb.23275
  • Peer Reviewed
• [Journal Article] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines (2011)
  • Author(s): Ito H., Yoshida K., Murakami M., Hagiwara K., Sasaki N., Kobayashi M., Takagi A., Kojima T., Sobue S., Suzuki M., Tamiya-Koizumi K., Nakamura M., Banno Y., Nozawa Y., Murate T.
  • Journal Title: Biochim. Biophys. Acta Volume: 1811 Issue: 3 Pages: 119-128
  • DOI: 10.1016/j.bbalip.2010.12.005
  • Peer Reviewed
• [Presentation] 急性呼吸窮迫症候群モデルマウスを用いた分子状水素の炎症軽減効果の検討 (2013)
  • Author(s): 祖父江沙矢加
  • Organizer: 第3回分子状水素医学シンポジウム
  • Place of Presentation: きゅりあん(東京都)
  • Year and Date: 2013-02-09
• [Presentation] Molecular hydrogen alters signaling pathways and gene expression profiles in multiple mouse organs (2012)
  • Author(s): Sayaka Sobue
  • Organizer: ASCB 2012
  • Place of Presentation: San Francisco(CA, USA)
  • Year and Date: 2012-12-18
• [Presentation] Egr-1 によるCD109 遺伝子の発現制御機構の解析 (2012)
  • Author(s): 祖父江沙矢加
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡県)
  • Year and Date: 2012-12-15
• [Presentation] 分子状水素のマウス肝臓における遺伝子発現とシグナル伝達への影響 (2012)
  • Author(s): 祖父江沙矢加
  • Organizer: 第2回分子状水素医学シンポジウム
  • Place of Presentation: 北里大学白金キャンパス薬学部コ ンベンションホール(東京都)
  • Year and Date: 2012-02-11
• [Presentation] 分子状水素のマウス肝臓における遺伝子発現とシグナル伝達への影響 (2012)
  • Author(s): 祖父江沙矢加
  • Organizer: 第2回分子状水素医学シンポジウム
  • Place of Presentation: 北里大学白金キャンパス薬学部コンベンションホール(東京都)
  • Year and Date: 2012-02-11
• [Presentation] Molecular hydrogen attenuates ERK and p38 MAPK-pathways and alters gene expressions in mouse liver and other organs (2011)
  • Author(s): Sayaka Sobue
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-16
• [Presentation] Overexpression of DNA dependent protein kinase (DNA-PK) in multidrug resistant leukemia cell line (2011)
  • Author(s): Misa Kobayasi
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-15
• [Presentation] The role of K-ras12A mutation in IL-2 independent growth of a LGL leukemia cell line, PLT-2 (2011)
  • Author(s): Naoki Mizutani
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-15
• [Presentation] 分子状水素投与に伴う肝臓内遺伝子発現変動の解析 (2011)
  • Author(s): 祖父江沙矢加
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2011-09-22
• [Presentation] Overexpressed sphingosine kinase 1 was decreased during HMBA-induced erythroid differentiation of Friend cells and the causative role of c-Myb (2011)
  • Author(s): 小林 美沙
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2011-09-22
• [Presentation] 分子状水素投与による肝保護効果の検討 (2011)
  • Author(s): Sayaka Sobue
  • Organizer: 分子状水素医学シンポジウ ム
  • Place of Presentation: 名古屋大学医学部附属病院(愛知県)
  • Year and Date: 2011-02-19
• [Presentation] 分子状水素投与による肝保護効果の検討 (2011)
  • Author(s): Sayaka Sobue
  • Organizer: 分子状水素医学シンポジウム
  • Place of Presentation: 名古屋大学医学部附属病院(愛知県)
  • Year and Date: 2011-02-19
• [Presentation] 水素水投与後の血中・臓器濃度と肝臓内酸化ストレス軽減効果の検討 (2010)
  • Author(s): Masatoshi Ichihara
  • Organizer: BMB2010
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2010-12-10
• [Presentation] cereulide毒素による肝障害に対する分子状水素の肝保護効果の検討 (2010)
  • Author(s): Sayaka Sobue
  • Organizer: BMB2010
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2010-12-08
• [Presentation] HMBA-induced erythroid differentiation decreases overexpressed SPHK1 in a mouse Friend cell line. (2010)
  • Author(s): Misa Kobayashi
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-24
• [Presentation] HMBA-induced erythroid differentiation decreases overexpressed SPHK1 in a mouse Friend cell line (2010)
  • Author(s): Misa Kobayasbi
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-24
• [Presentation] Egr-1によるCD109遺伝子の発現制御機構の解析
  • Author(s): 祖父江沙矢加
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Molecular hydrogen alters signaling pathways and gene expression profiles in multiple mouse organs.
  • Author(s): Sobue S
  • Organizer: ASCB 2012
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] 急性呼吸窮迫症候群モデルマウスを用いた分子状水素の炎症軽減効果の検討
  • Author(s): 祖父江沙矢加
  • Organizer: 第3回分子状水素医学シンポジウム
  • Place of Presentation: きゅりあん（東京）