Involvement of Akt/mTOR in lung cancer and design of novel therapy targeting them

2017 Fiscal Year Final Research Report

• Project/Area Number: 26460438
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Jichi Medical University
• Principal Investigator: DOBASHI Yoh 自治医科大学, 医学部, 准教授 (90231456)
• Co-Investigator(Kenkyū-buntansha): 北川 雅敏 浜松医科大学, 医学部, 教授 (50294971) ; 坪地 宏嘉 自治医科大学, 医学部, 教授 (50406055) ; 後藤 明輝 秋田大学, 医学(系)研究科(研究院), 教授 (90317090)
• Co-Investigator(Renkei-kenkyūsha): OOI Akishi 金沢大学, 医学部, 教授 (50160411) ; SUGIMURA Haruhiko 浜松医科大学, 医学部, 教授 (00196742) ; MATSUBARA Hirochika 山梨大学, 医学部, 講師 (00374166)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 肺癌 / Akt / 遺伝子増幅 / microRNA / p27 / MLPA / Ubiquitin ligase

Outline of Final Research Achievements

We analyzed the involvement of Akt in lung carcinomas. Results were, i) Microarray analysis revealed 28 miRNAs upregulated in AKT1 or AKT2-amplified carcinomas, including miR-200. Carcinomas with lymph vessel invasion had lower expression of miR-200a/b and in adenocarcinoma and in the early carcinomas, miR-200a was higher in AKT2-amplified group. MiR-200a was significantly correlated with the expression of its target, EphA. ii) Expressions of p27 and ubiquitin ligase Skp2, KPC and Pirh2 were analyzed. Cytoplasmic p27 was correlated with nodal metastasis and, inverse correlation between nuclear-p27 and Pirh2 was observed. Moreover, Pirh2 was correlated with Stage and overall survival. iii) We performed multiplex ligation-dependent probe amplification (MLPA) analysis with fluorescence in situ hybridization analysis and immunohistochemistry. By placing modified cutoff values, cases containing fewer cancer cells with gene increase could be picked up by MLPA using custom-made probes.

Free Research Field

人体病理学