Comprehensive analysis of novel genes regulating the malignant transformation in small-sized lung adenocarcinoma

• Project/Area Number: 21390390
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Hiroshima University
• Principal Investigator: OKADA Morihito 広島大学, 原爆放射線医科学研究所, 教授 (70446045)
• Co-Investigator(Kenkyū-buntansha): ITO Akihiko 近畿大学, 医学部, 教授 (80273647)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2009: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 腫瘍学 / 小型肺がん / 肺胞上皮癌 / 肺腺癌 / 肺がん / がん悪性度診断

Research Abstract

The transcription factors Notch2 and Six1 were upregulated in invasive cancer cells in all minimally invasive adenocarcinomas. Exogenous Notch2 transactivated Six1 followed by Smad3, Smad4, and vimentin, and enlarged the nuclei of NCI-H441 lung epithelial cells. Immunochemical staining for the transcription factors was double positive in the invasive, but not in the lepidic growth component of a third of advanced Ads, and the disease-free survival rates were lower in such tumors. Paired upregulation of Notch2 and Six1 is a transcriptional aberration that contributes to preinvasive-to-invasive adenocarcinoma progression by inducing epithelial-mesenchymal transition and nuclear atypia. This aberration persisted in a considerable subset of advanced adenocarcinoma and conferred a more malignant phenotype on the subset

Research Products

• [Journal Article] Upregulation of notch2 and six1 is associated with progression of early-stage lung adenocarcinoma and a more aggressive phenotype at advanced stages (2012)
  • Author(s): Mimae T, Okada M, Hagiyama M, MiyataY, Tsutani Y, Inoue T, Murakami Y, ItoA
  • Journal Title: Clinical Cancer Research Volume: 18(4) Pages: 945-55
  • Peer Reviewed
• [Journal Article] Upregulation of Notch2 and Six1 Is Associated with Progression of Early-Stage Lung Adenocarcinoma and a More Aggressive Phenotype at Advanced Stages (2012)
  • Author(s): Mimae T, Okada M, Hagiyama M, Miyata Y, Tsutani Y, Inoue T, Murakami Y, Ito A
  • Journal Title: Clinical Cancer Research Volume: 18 Pages: 945-55
  • Peer Reviewed
• [Presentation] Notch2 and Six1 are upregulated duringprogression of early-stage lung adenocarcinoma and define its unfavorable subset at advanced stages (2012)
  • Author(s): Takahiro Mimae, Morihito Okada, ManHagiyama, Yoshihiro Miyata, YasuhiroTsutani, Takao Inoue, Kenjiro Aogi, Yoshinori Murakami, Akihiko Ito
  • Organizer: American Association of Cancer Research(AACR) Annual Meeting 2012
  • Place of Presentation: Chicago, USA