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Chronic stress promotes lung cancer development via IGF-1R pathway : 만성적인 스트레스가 폐암 발생에 미치는 영향 연구
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 이호영 | - |
dc.contributor.author | Jang Hyun-Ji | - |
dc.date.accessioned | 2017-07-19T11:21:53Z | - |
dc.date.available | 2017-07-19T11:21:53Z | - |
dc.date.issued | 2015-08 | - |
dc.identifier.other | 000000067249 | - |
dc.identifier.uri | https://hdl.handle.net/10371/133603 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 약학과(병태생리학), 2015. 8. 이호영. | - |
dc.description.abstract | Lung cancer is a leading cause of cancer-related death worldwide. Although smoking is a main cause, approximately 25% of lung cancer cases are not attributable to tobacco use. Although various risk factors, including Radon, ETS(Environmental Tobacco Smoke), genetic and viral factors, have been implicated in the pathogenesis of lung cancer in never smokers, this study suggests that chronic stress is also one of the risk factors. Recent mechanistic studies demonstrate that chronic stress is associated with the progression of various cancer types. But the underlying mechanisms for the association between chronic stress and lung cancer development are poorly understood.
Stress hormone, norepinephrine (NE)-induced activation of beta-adrenergic receptor(ADBR) pathway is involved in various cellular process including cancer onset, cancer progression, inflammation, angiogenesis and immune system. We observed that a continuous exposure of NE induced transformation of human lung bronchial epithelial cells and activated type-1 in-sulin-like growth factor receptor (IGF-IR) signaling pathway. To examine the effect of chronic stress on lung cancer for-mation in vivo, we established CUS(Chronic unpredictable stress) mouse model. We found that chronic stress resulted in high levels of NE in mouse serum, activation of IGF-IR in lung tissue and promoted lung tumor formation. Moreover, we confirmed that inhibition of the IGF-IR pathway suppressed NE-induced cell transformation in vitro. To investigate the mechanism underlying the NE-induced activation of IGF-IR pathway, we first analyzed expression level of IGF-IR axis in human lung bronchial epithelial cell lines. We confirmed that NE-induced IGF-IR activation was occurred in cell line with high-expression of IGF-II. Treatment of NE increased intracellular calcium level thought beta adrenergic receptor pathway and induced calcium-mediated secretion of IGF-II protein. Also, we showed that IGF-BP3 which regulates function of IGF-II protein is downregulated by treating NE. In conclusion, NE increased availability of IGF-II and then activated IGF-IR pathway. Our results indicate that stress hormone, NE may pro-mote lung cancer development via the IGF-IR pathway, sug-gesting that blockade of IGF-IR is important for controlling chronic stress-promoted lung cancer development | - |
dc.description.tableofcontents | Contents
ABSTRACT i CONTENTS iv LIST OF TABLES vi LIST OF FIGURES vii I. INTRODUCTION 1 II. MATERIALS AND METHODS 6 Chemicals and reagent 6 Cell lines, culture conditions 6 MTT assay 7 Anchorage dependent/Soft agar assay 7 Foci formation assay 9 Flow cytometry assay 9 siRNAs and transfection 10 Western blot 10 Animal experiment for chronic stress 12 MMP florescence combining CT imaging 13 Immunostaining assay 13 Tumor multiplicity and volume 14 III. RESULT 15 IV. DISCUSSION 40 REFERENCES 45 국문초록 52 | - |
dc.format | application/pdf | - |
dc.format.extent | 1531468 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | 스트레스 | - |
dc.subject | 폐암 | - |
dc.subject.ddc | 615 | - |
dc.title | Chronic stress promotes lung cancer development via IGF-1R pathway | - |
dc.title.alternative | 만성적인 스트레스가 폐암 발생에 미치는 영향 연구 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | 장현지 | - |
dc.description.degree | Master | - |
dc.citation.pages | viii, 53 | - |
dc.contributor.affiliation | 약학대학 약학과 | - |
dc.date.awarded | 2015-08 | - |
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