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)
|
Co-Investigator(Kenkyū-buntansha) |
筆宝 義隆 国立研究開発法人国立がん研究センター, 研究所, 客員研究員 (30359632)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
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.
|