2016 Fiscal Year Final Research Report
Defining the KRAS signaling cascade using a genome-edited human bronchial epithelial cell line
| Project/Area Number |
25460395
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | KRAS / 変異ノックイン / 気管支上皮細胞株 |
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| Outline of Final Research Achievements |
The KRAS gene is mutated and constitutively activated in many types of cancers including lung cancer. In this study, we utilized a non-tumorigenic human bronchial epithelial cell line which had undergone targeted knock-in of an oncogenic KRAS mutation to investigate the biological function of the mutant KRAS gene. We found that the mutant KRAS induced an altered cellular morphology similar to cancer cells, conferred the capacity of anchorage-independent cell growth, and augmented cell migration and invasion into Matrigel. The MEK-ERK pathway which promotes cell proliferation was hyperactivated in the mutant KRAS-knocked-in cells. Comprehensive analysis of mRNA and protein expression in the cells revealed the increased expression of some molecules potentially explaining the transformed phenotype seen in the mutant KRAS-knocked-in cells. This study helps us to understand the biological function of mutant KRAS and will assist in the development of medicine for KRAS-mutated cancers.
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| Free Research Field |
がんの分子生物学的研究
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