Analysis of AMF and its related proteins in lung cancer

• Project/Area Number: 15K10270
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Jichi Medical University
• Principal Investigator: TSUBOCHI Hiroyoshi 自治医科大学, 医学部, 教授 (50406055)
• Co-Investigator(Kenkyū-buntansha): 遠藤 俊輔 自治医科大学, 医学部, 教授 (10245037) ; 遠藤 哲哉 昭和大学, 医学部, 講師 (50528601)
• Research Collaborator: DOBASHI yoh
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肺癌 / AMF / Akt / p27 / 非小細胞肺癌 / Skp2 / KPC / Pirh 2 / 予後 / AKT遺伝子 / 自立型細胞運動刺激因子 / 上皮成長因子受容体 / 自律型細胞運動刺激因子

Outline of Final Research Achievements

Immunohistochemical staining for 108 cases revealed overexpression of total Akt, Akt1, Akt2 and Akt3 in 61.1, 47.2, 40.7 and 23.1%, respectively, and phosphorylated Akt in 42.6% of cases.Expression of total Akt, Akt2 and Akt3 were frequently observed in small cell carcinoma, but phosphorylated Akt and Akt1 were more frequently observed in squamous cell carcinoma.Although "FISH-positive" AKT1 and AKT2 gene increases (amplification/high-level polysomy) were found exclusively in the cases overexpressing total Akt, Akt1 or Akt2, respectively, AKT3 increase was irrelevant of Akt3 expression. Statistically, expressions of Akt2, p-Akt and cytoplasmic-p-Akt were correlated with lymph node metastasis . Although AKT1 and AKT2 gene increase showed positive correlation with, or trend towards a positive correlation with tumor size , AKT3 did not.

Academic Significance and Societal Importance of the Research Achievements

肺癌において、EGFR-Aktの相互関係、制御機構の意義を推定することができ、肺癌症例の層別化、個別化に結び付くことが期待される。さらに、臨床Stage分類では予見できない進展の早い癌、術後早期再発例を抽出することで、癌症例の更なる細分化につながる可能性がある。

Research Products

• [Journal Article] Regulation of p27 by ubiquitin ligases and its pathological significance in human lung carcinomas (2017)
  • Author(s): Dobashi Y, Tsubochi H, Minegishi K, Kitagawa M, Otani S, Ooi A.
  • Journal Title: Human Pathology Volume: 66 Pages: 67-68
  • DOI: 10.1016/j.humpath.2017.05.022
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNAs associated with increased AKT gene number in human lung carcinoma. (2016)
  • Author(s): Goto A, Dobashi Y, Tsubochi H, Maeda D, Ooi A
  • Journal Title: Hum Pathol Volume: 印刷中 Pages: 1-10
  • DOI: 10.1016/j.humpath.2016.04.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diverse involvement of isoforms and gene aberrations of Akt in human lung carcinomas (2015)
  • Author(s): Dobashi Y, Tsubochi H, Matsubara H, Inoue J, Inazawa J, Endo S, Ooi A
  • Journal Title: Cancer Sci Volume: - Issue: 6 Pages: 772-781
  • DOI: 10.1111/cas.12669
  • Peer Reviewed / Open Access / Acknowledgement Compliant