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Investigation of Molecular Mechanisms of Apoptosis using gene knock-out leukemic cell lines

Research Project

Project/Area Number 20591261
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKitasato University

Principal Investigator

MIYASHITA Toshiyuki  Kitasato University, 医学部, 教授 (60174182)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアポトーシス / グルココルチコイド / RCAN1 / 白血病 / 相同組換え / カスパーゼ
Research Abstract

In order to investigate the molecular mechanism of how glucocorticoid (GC) induces apoptosis in certain leukemic cells, we established RCAN1 gene knock-out Nalm6 cells. RCAN1 is one of the target genes of GC and Nalm6 is a human leukemic cell line that undergoes apoptosis upon the treatment with GC. RCAN1 -/- cells were markedly resistant to GC compared with wild-type cells. On the contrary, overexpression of RCAN1 resulted in enhanced apoptosis by GC. These resultsdemonstrate that RCAN1 is a mediator for GC-induced apoptosis in leukemic cells.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (43 results)

All 2011 2010 2009 2008 Other

All Journal Article (20 results) (of which Peer Reviewed: 17 results) Presentation (17 results) Book (2 results) Remarks (4 results)

  • [Journal Article] Entire PTCH1 deletion is a common event in point mutation-negative cases with nevoid basal cell carcinoma syndrome in Japan.2011

    • Author(s)
      Nagao K., Fujii K., Saito K., Sugita K., Endo M., Motojima T., Hatsuse H., Miyashita T.
    • Journal Title

      Clin.Genet. 79

      Pages: 196-198

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Entire PTCH1 deletion is a common event in point mutation-negative cases with nevoid basal cell carcinoma syndrome in Japan.2011

    • Author(s)
      Miyashita, T.
    • Journal Title

      Clin.Genet.

      Volume: 79 Pages: 196-198

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 見逃してはいけない家族性腫瘍:本邦における母斑基底細胞癌症候群の遺伝子変異と臨床的特徴2011

    • Author(s)
      宮下俊之
    • Journal Title

      家族性腫瘍

      Volume: 11 Pages: 14-18

    • NAID

      130007529694

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple keratocystic odontogenic tumors associated with nevoid basal cell carcinoma syndrome having distinct PTCH1 mutations : a case report.2010

    • Author(s)
      Sasaki R., Miyashita T., Matsumoto N., Fujii K., Saito K., Ando T.
    • Journal Title

      Oral Surg.Oral Med.Oral Pathol.Oral Radiol.Endod. 110

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blasts in transient leukemia in neonates with Down syndrome differentiate into basophil/mast-cell and megakaryocyte lineages in vitro in association with down-regulation of truncated form of GATA1.2010

    • Author(s)
      Miyauchi J., Ito Y., Tsukamoto K., Takahashi H., Ishikura K., Sugita K., Miyashita T.
    • Journal Title

      Brit.J.Haematol. 148

      Pages: 898-909

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ヘッジホッグと形態形成-Gorlin症候群とPTCH遺伝子変異-2010

    • Author(s)
      藤井克則,宮下俊之
    • Journal Title

      日本小児皮膚科学会雑誌 28

      Pages: 65-71

    • NAID

      10026418020

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] グルココルチコイド受容体2010

    • Author(s)
      宮下俊之
    • Journal Title

      日本薬理学会誌 135

      Pages: 117-118

    • NAID

      10026334909

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple keratocystic odontogenic tumors associated with nevoid basal cell carcinoma syndrome having distinct PTCH1 mutations : a case report.2010

    • Author(s)
      Miyashita, T.
    • Journal Title

      Oral Surg.Oral Med.Oral Pathol.Oral Radiol.Endod.

      Volume: 110

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Blasts in transient leukemia in neonates with Down syndrome differentiate into basophil/mast-cell and megakaryocyte lineages in vitro in association with down-regulation of truncated form of GATAl.2010

    • Author(s)
      Miyashita, T.
    • Journal Title

      Brit.J.Haematol. 148

      Pages: 898-909

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nevoid basal cell carcinoma syndrome with cleft lip and palate associated with the novel PTCH gene mutations.2009

    • Author(s)
      Sasaki R., Saito K., Watanabe Y., Miyashita T., Fujii K., Agawa K., Takayama Y., Ando T., Akizuki, T.
    • Journal Title

      J.Hum.Genet. 54

      Pages: 398-402

    • NAID

      10030731005

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] EYA4, Deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally.2009

    • Author(s)
      Abe Y., Oka A., Mizuguchi M., Igarashi T., Ishikawa S., Aburatani H., Yokoyama S., Asahara H., Nagao K., Yamada M., Miyashita T.
    • Journal Title

      Hum.Mutat. 30

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ヘッジホッグと形態形成-発生生物学から臨床医学への応用-2009

    • Author(s)
      藤井克則,宮下俊之
    • Journal Title

      脳と発達 41

      Pages: 247-252

    • NAID

      10024846234

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gorlin症候群における臨床的検討-主要症状を中心とした多様な症候スペクトラム-2009

    • Author(s)
      田辺良,藤井克則,宮下俊之,他
    • Journal Title

      脳と発達 41

      Pages: 253-257

    • NAID

      10024846296

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gorlin症候群における分子遺伝学的検討-PTCH1遺伝子変異とその多様な変異スペクトラム-2009

    • Author(s)
      遠藤真美子,藤井克則,宮下俊之,他
    • Journal Title

      脳と発達 41

      Pages: 259-263

    • NAID

      10024846313

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally.2009

    • Author(s)
      Miyashita, T.
    • Journal Title

      Hum.Mutat. 30

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nevoid basal cell carcinoma syndrome with cleft lip and palate associated with the novel PTCH gene mutations.2009

    • Author(s)
      Miyashita, T.
    • Journal Title

      J.Hum.Genet. 54

      Pages: 398-402

    • NAID

      10030731005

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Patched1 haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity.2008

    • Author(s)
      Ohba S., Kawaguchi H., Kugimiya F., Ogasawara T., Kawamura N., Saito T., Ikeda T., Fujii K., Miyajima T., Kuramochi A., Miyashita T., Oda H., Nakamura K., Takato T., Chung, U.I.
    • Journal Title

      Dev.Cell 14

      Pages: 689-699

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ステロイドの抗腫瘍作用マイクロアレイを用いた作用機序の解析2008

    • Author(s)
      宮下俊之,押田忠弘
    • Journal Title

      日本臨床 66

      Pages: 89-93

    • Related Report
      2010 Final Research Report
  • [Journal Article] Patchedl haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity.2008

    • Author(s)
      Ohba S, Miyashita T
    • Journal Title

      Dev. Cell 14

      Pages: 689-699

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ステロイドの抗腫瘍作用-マイクロアレイを用いた作用機序の解析-2008

    • Author(s)
      宮下 俊之
    • Journal Title

      日本臨床 66

      Pages: 89-93

    • Related Report
      2008 Annual Research Report
  • [Presentation] 母斑基底細胞癌症候群の約16%がPTCH1遺伝子全欠損で発症する2010

    • Author(s)
      長尾和右,桐生麻衣子,高山吉永,宮下俊之
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] ヘッジホッグシグナル伝達経路に抑制的に働く抗PTCH1マウスモノクロナル抗体の作製2010

    • Author(s)
      高山吉永,長尾和右,桐生麻衣子,宮下俊之
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] 日本人母斑基底細胞癌症候群の16%はPTCH1遺伝子の片アレル欠損で発症する2010

    • Author(s)
      宮下俊之,長尾和右,遠藤真美子,本島敏乃,齋藤加代子,杉田克生,藤井克則
    • Organizer
      第16回日本家族性腫瘍学会学術集会
    • Place of Presentation
      新潟
    • Related Report
      2010 Final Research Report
  • [Presentation]2010

    • Author(s)
      宮下俊之,遠藤真美子,齋藤加代子,杉田克生,藤井克則
    • Organizer
      第16回日本家族性腫瘍学会学術集会
    • Place of Presentation
      新潟
    • Related Report
      2010 Final Research Report
  • [Presentation] 母斑基底細胞癌症候群症例の16%がPTCH1遺伝子の全欠失によって発症する2010

    • Author(s)
      長尾和右,高山吉永,亀山孝三,宮下俊之
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒトPatched1(PTCH1)レセプターに対して作製したマウスモノクロナル抗体の評価2010

    • Author(s)
      高山吉永,志村将人,桐生麻衣子,長尾和右,亀山孝三,宮下俊之
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] 本邦における母斑基底細胞癌症候群の遺伝子変異と臨床的特徴2010

    • Author(s)
      宮下俊之
    • Organizer
      第16回日本家族性腫瘍学会学術集会
    • Place of Presentation
      朱鷺メッセ(新潟県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヘッジホッグシグナル伝達経路に抑制的に働く抗PTCH1マウスモノクロナル抗体の作製2010

    • Author(s)
      宮下俊之
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 母斑基底細胞癌症候群症例の16%がPTCH1遺伝子の全欠失によって発症する2010

    • Author(s)
      宮下俊之
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 6番染色体長腕に欠損を認めた全前脳胞症亜型における原因遺伝子についての検討2009

    • Author(s)
      阿部裕一、島田隆史、古山晶子、星野英紀、久保田雅也、宮下俊之、岡明
    • Organizer
      第51回日本小児神経学会総会
    • Place of Presentation
      米子
    • Related Report
      2010 Final Research Report
  • [Presentation] 多発性顎嚢胞を契機に診断したPTCH遺伝子異常を伴った基底細胞母斑症候群2009

    • Author(s)
      佐々木亮、齋藤加代子、宮下俊之、渡辺頼勝、藤井克則、阿川かおり、高山吉永、秋月種高、安藤智博
    • Organizer
      第15回日本家族性腫瘍学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] FKBP5ノックアウト細胞株を用いたアポトーシス誘導機序の解析2009

    • Author(s)
      長尾和右、山田正夫、宮下俊之
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] FKBP5ノックアウト白血病細胞株を用いたグルココルチコイドによるアポトーシス誘導機序の解析2009

    • Author(s)
      長尾和右、宮下俊之
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 全前脳症原因候補遺伝子としてのEYA4に関する検討2008

    • Author(s)
      阿部裕一、石川俊平、油谷浩幸、横山成俊、浅原弘嗣、山田正夫、岡明、五十嵐隆、宮下俊之
    • Organizer
      第31回日本分子生物学会年会・第80回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] PTCH1遺伝子領域を含むゲノム欠損による母斑基底細胞癌症候群3例の解析2008

    • Author(s)
      宮下俊之、藤井克則
    • Organizer
      第14回日本家族性腫瘍学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Nevoid basal cell careinoma syndrome with cleft lip and palate associated with mutation of the PTCH gene : report of two cases2008

    • Author(s)
      Sasaki R, Miyashita T
    • Organizer
      XIX Congress of the European Association for Cranio-MaXillo-Facial Surgery
    • Place of Presentation
      Bologna, Italy
    • Related Report
      2008 Annual Research Report
  • [Presentation] 全前脳症原因候補遺伝子としてのEYA4に関する検討2008

    • Author(s)
      阿部裕一, 宮下 俊之
    • Organizer
      第31回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Book] メディカル・サイエンス・インターナショナル(症例でわかる新臨床遺伝学 水谷修紀 監訳)2008

    • Author(s)
      宮下俊之(分担翻訳)
    • Related Report
      2010 Final Research Report
  • [Book] 症例でわかる新臨床遺伝学(分担翻訳)2008

    • Author(s)
      Andrew Read宮下 俊之
    • Total Pages
      431
    • Publisher
      メディカル・サイエンス・インターナショナル
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.med.kitasato-u.ac.jp/~molgen/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.med.kitasato-u.ac.jp/~molgen/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kitasato-u.ac.jp/~molgen/index.html

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kitasato-u.ac.jp/~molgen/sub3.html

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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