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Development of novel molecular-target therapy focus on type I, type II uterine endometrial cancer

Research Project

Project/Area Number 21791562
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionKyushu University

Principal Investigator

INOUE Takafumi  Kyushu University, 大学病院, 助教 (70380417)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords子宮体がん / アポトーシス / 活性酸素種 / senescence / apoptosis / I型、II型子宮体癌 / K-ras / 分子標的治療
Research Abstract

Objectives : Increased expression level of p21 induced by p53 is one of the molecular target of premature senescence. Reactive oxygen species (ROS) is involved in this process. In this study, we investigated how ROS is mediated with the cell growth and mechanism of cellular senescence by suppressed ER using the model of NIH3T3 cell transformed by oncogenic K-ras.
Materials and Methods : 1) We established two NIH3T3 cell lines that expressed only oncogenic K-ras (K12V) or co-expressed dominant negative ER (K12VDNER) and analyed the cell growth. 2) Induction of senescence was evaluated by β-gal staining. Intracellular levels of ROS were measured by FACS using Aminophenyl fluorescin (APF). 3) Inhibitor of ROS, N-acetyl -L-cystein (NAC), was added onto the cell lines, and effect against the induction of senescence was evaluated. 4) Several proteins related with ras signaling was evaluated with immunoblots.
Results : 1) Cell growth of K12VDNER cells were markedly suppressed compared to mock or K12V cells accompanied with senescence by the appearance of multi-nucleated flat cells and significant increase of positive β-gal staining. 3) Intracellular levels of ROS were increased about two times in K12VDNER cells accompanying with induction of senescence. 3) In K12VDNER cell, positive β-gal staining cells were decreased and cell growth was recovered by the addition of NAC. 4) Expression level of p21 was increased in K12VDNER cell compared to mock or K12V cell.
Conclusion : Cellular senescence mediated with oncogenic K-ras and ER related with ROS. We suggested the pathway of senescence via ROS because inhibition of ROS rescued the induction of senescence.

Report

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

    (7 results)

All 2010 2009 Other

All Journal Article (5 results) (of which Peer Reviewed: 3 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers.2010

    • Author(s)
      Tatsuhiro Ohgami, Takafumi Inoue, et.al.
    • Journal Title

      Cancer Science 101

      Pages: 1387-1395

    • Related Report
      2010 Final Research Report
  • [Journal Article] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers.2010

    • Author(s)
      Tatsuhiro Ohgami, et.al.
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 1387-1395

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers.2010

    • Author(s)
      Tatsuhiro Ohgami, et. al.
    • Journal Title

      Cancer Science (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Level of Reactive Oxygen Species inducedby p21WAF1/CIP1 is critical for the determination of cell fate.2009

    • Author(s)
      Takafumi Inoue, et.al.
    • Journal Title

      Cancer Science 100

      Pages: 1275-1283

    • Related Report
      2010 Final Research Report
  • [Journal Article] The Level of Reactive Oxygen Species induced by p21^<WAF1/CIP1> is critical for the determination of cell fate.2009

    • Author(s)
      Takafumi Inoue, et. al.
    • Journal Title

      Cancer Science 100

      Pages: 1275-1283

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 活性化型K-rasとestrogen receptor(ER)が関与する細胞内活性酸素種を介した細胞老化誘導能に関する検討2010

    • Author(s)
      井上貴史
    • Organizer
      第61回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京都
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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