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Establishment of for evaluation model of pathological subtypes in lung adenocarcinoma using organoid culture and investigation of formation mechanism

Research Project

Project/Area Number 19K07414
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionTottori University

Principal Investigator

SAKABE Tomohiko  鳥取大学, 医学部, 助教 (50639747)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords浸潤性肺腺癌 / 充実型増殖部 / RNA-Seq / 転写因子 / 充実型亜型 / IASLC/ATS/ERS分類 / 膜タンパク / 組織亜型分類 / 腺房型亜型 / オルガノイド培養法 / 組織亜型
Outline of Research at the Start

本研究は、オルガノイド培養法による浸潤性肺腺癌の組織亜型形成が検証可能なモデルマウスを樹立することで、予後不良なhigh grade亜型形成に関わる重要な因子を同定し、形成メカニズムを解明することを目的としている。具体的には以下の項目について検討する。
1. マウス初代培養肺細胞を用いた肺オルガノイドの作製
2. 肺腺癌ドラバー変異導入によるin vitro発癌モデルの樹立と亜型形成評価
3. 候補遺伝子導入によるhigh grade亜型誘導と形成メカニズム解明

Outline of Final Research Achievements

In this study, we aimed to elucidate the mechanism of pathological subtype formation in invasive lung adenocarcinoma (LUAD). Comparison of gene expression profiles between acinar component and solid component identified 1,272 differentially expressed genes in solid component. Genes involved in cell proliferation were abundant among the upregulated genes, and their expression profiles were consistent with the pathological findings in solid component. Additionally, 10 transcription factors were extracted by in silico analysis that seem to be involved in the regulation of solid component. Among them, four transcription factors significantly increased cell proliferation in LUAD cell lines, suggesting that these transcription factors are involved in the formation and maintenance of solid component in LUAD.

Academic Significance and Societal Importance of the Research Achievements

浸潤性肺腺癌において、充実型増殖部を含む一部の病理学的組織亜型の存在は患者予後不良と相関を示すことが報告されているが、その形成機序は未だ不明であり、特異的な治療も存在していない。本研究で明らかにした充実型増殖部の病理所見と一致する遺伝子発現プロファイルは、新たな観点に基づいた肺腺癌治療法開発の基盤になると考えている。さらに、実際に同定した転写因子が肺腺癌の増殖能を増加させたことから、治療標的として有用であると推測でき、今後さらなる研究を重ねることで新規治療法開発へと応用できることが期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (1 results)

All 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Gene expression profiling by targeted RNA sequencing in pathological stage I lung adenocarcinoma with a solid component2020

    • Author(s)
      Kidokoro Yoshiteru、Sakabe Tomohiko、Haruki Tomohiro、Kadonaga Taichi、Nosaka Kanae、Nakamura Hiroshige、Umekita Yoshihisa
    • Journal Title

      Lung Cancer

      Volume: 147 Pages: 56-63

    • DOI

      10.1016/j.lungcan.2020.06.035

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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