Molecular analysis of tumor suppressor gene NDRG2 function and regulation of expression

• Project/Area Number: 25860242
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: University of Miyazaki
• Principal Investigator: ICHIKAWA Tomonaga 宮崎大学, 医学部, 助教 (80586230)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌 / シグナル伝達 / ストレス / 成人病

Outline of Final Research Achievements

We reported that novel tumor suppressor gene NDRG2 (N-myc downstream-regulated gene 2) regulate signal transduction of PI3K/AKT and NF-kappaB (NFκB) pathway through the suppression of PTEN phosphorylation, resulting in the involvement of tumorigenesis. We demonstrated that transient stress response including inflammation induces NDRG2 expression via NFκB pathway. Therefore, the transient stress-induced signal transduction is negatively feedback regulated by NFκB-induced NDRG2 expression. Furthermore, chronic stress promotes the own-regulation of NDRG2 through DNA promoter methylation. These finding suggest that elucidating the mechanism of NDRG2 function and regulation of expression may become a new therapeutic target for many type of disease.

Research Products

• [Journal Article] Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers. (2014)
  • Author(s): Nakahata S, Ichikawa T, Maneesaay P, Saito Y, Nagai K, Tamura T, Manachai N, Yamakawa N, Hamasaki M, Kitabayashi I, Arai Y, Kanai Y, Taki T, Abe T, Kiyonari H, Shimoda K, Ohshima K, Horii A, Shima H, Taniwaki M, Yamaguchi R, Morishita K.
  • Journal Title: Nat Commun Volume: in press Issue: 1 Pages: 3393-3393
  • DOI: 10.1038/ncomms4393
  • Peer Reviewed / Open Access
• [Presentation] PTENリン酸化異常におけるATLがん発症機構 (2015)
  • Author(s): 市川 朝永
  • Organizer: 第19回造血器腫瘍研究会
  • Place of Presentation: グランデはがくれ (佐賀県)
  • Year and Date: 2015-01-22 – 2015-01-23
• [Presentation] Ndrg2 deficient mice improve depressive behavior through the activation of AKT signaling. (2014)
  • Author(s): 市川 朝永
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 国立京都国際会館 (京都府)
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] N-myc down-regulated gene 2 suppresses NF-kB as a PP2A recruiter for defending constitutive activation of NF-kB after HTLV-1 infection. (2014)
  • Author(s): 市川 朝永
  • Organizer: 第73回日本癌学会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ATLにおける新規PTENキナーゼの同定と機能解析 (2014)
  • Author(s): 市川 朝永
  • Organizer: 第1回HTLV-1学会
  • Place of Presentation: 東京大学医科学研究所講堂 (東京都)
  • Year and Date: 2014-08-23 – 2014-08-24
• [Presentation] がん抑制遺伝子NDRG2によるHTLV-1/Tax誘導性NF-kB活性抑制機構の解析 (2013)
  • Author(s): 市川 朝永
  • Organizer: 第34回日本炎症・再生医学会
  • Place of Presentation: 国立京都国際会館 (京都府)
• [Presentation] NDRG2はPP2AリクルーターとしてPTEN及びNIK活性調節に関わる (2013)
  • Author(s): 市川 朝永
  • Organizer: 第6回HTLV-1研究会
  • Place of Presentation: 東京大学医科学研究所講堂 (東京都)
• [Presentation] Molecular mechanisms of 4-nitroquinoline 1-oxide(4-NQO)-induced oral carcinogenesis in NDRG2-deficient mice (2013)
  • Author(s): 市川 朝永
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
• [Presentation] Molecular mechanisms of 4-nitroquinoline 1-oxide(4-NQO)-induced oral carcinogenesis in NDRG2-deficient mice (2013)
  • Author(s): 市川 朝永
  • Organizer: 第72回日本癌学会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
• [Presentation] NDRG2はPP2AリクルーターとしてPTEN及びNIK活性調節に関わる
  • Author(s): 市川 朝永
  • Organizer: 第18回造血器腫瘍研究会
  • Place of Presentation: がん研究会がん研究所吉田富三記念講堂(東京都)