Lung carcinogenesis by genetic reconstitution using organoids derived from normal lung in mice

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Ochiai Masako 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (90150200)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 正常肺３Ｄ培養 / in vitro肺発がんモデル

Outline of Final Research Achievements

We aimed to establish the 3D-cultured cells (organoids) from normal lung tissues in mice and to construct an in vitro model of lung carcinogenesis using genetic reconstitution, which is transduction by shRNAs of tumor suppressor genes (TSG) using lentivirus. From the examination of culture conditions, it was suitable for lung organoids culture to the addition of inhibitor X related to a signal transduction and growth factor Y with proliferative effect for alveolar cells type II. These organoids with transduction of TSG shRNAs were injected to nude mice subcutaneously and developed tumors.
In application to in vitro evaluation system of lung carcinogenesis by chemicals, lung carcinogen C as positive control is possible dose setting in the combination to chemical exposure. After multiple exposures, it was formed subcutaneous tumor in nude mice and it was shown to dysplastic features. It is indicated that dysplastic changes can be an marker for carcinogenic potentials of chemicals.

Free Research Field

環境発がん