2015 Fiscal Year Final Research Report
The potential mechanisms of EGFR-TKI induced lung injury in mice model
| Project/Area Number |
25870736
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
Tumor biology
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 上皮成長因子受容体阻害剤 / 腫瘍壊死因子 / 肺障害 |
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| Outline of Final Research Achievements |
Epidermal Growth Factor Receptor (EGFR) and other ErbB receptors; ErbB2-4, through cytokine and growth factor stimulation, are up-regulated in lung emphysema, pulmonary fibrosis and lung cancer, suggesting that the activation of ErbB receptors is response to emphysema, fibrosis and cancer in humans. TNF is a major inflammatory cytokine with many biological properties including both anti- and pro-apoptotic signaling pathways. However, the molecular switch, which determines TNF regulation of these two different functions, is not well characterized. We previously reported that EGFR and ErbB2 were transactivated by TNF via SRC kinase activity, which promotes the intestinal epithelial cell survival response to TNF. In this study, we elucidate the hypothesis that EGFR/ErbBs activity regulates TNF-mediated bronchial epithelial cell survival and inhibition of EGFR tyrosine kinase activity increase bronchial epithelial cell apoptosis, then finally fibrosing lung tissues in SP-C/TNF tg mice.
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| Free Research Field |
呼吸器内科学
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