새로운 간세포 성장인자 수용체 변이형의 암화 억제 능력

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dc.contributor.advisor이재호-
dc.contributor.author이복순-
dc.date.accessioned2018-11-08T06:28:24Z-
dc.date.available2018-11-08T06:28:24Z-
dc.date.issued2009-08-
dc.identifier.other10018-
dc.identifier.urihttps://dspace.ajou.ac.kr/handle/2018.oak/3270-
dc.description학위논문(박사)--아주대학교 일반대학원 :분자과학기술학과,2009. 8-
dc.description.tableofcontentsTABLE OF CONTENTS ABSTRACT----------------------------------------------------------------------------------------------ⅰ TABLE OF CONTENTS-----------------------------------------------------------------------------ⅲ LIST OF FIGURES------------------------------------------------------------------------------------ⅴ LIST OF TABLES-------------------------------------------------------------------------------------ⅶ Ⅰ. INTRODUCTION----------------------------------------------------------------------------------1 A. Structure of Met receptor tyrosine kinase------------------------------------------------------------1 B. Aberrant activation of HGF-Met signaling in cancers---------------------------------------------3 C. Therapeutic strategies targeting Met in human cancers-------------------------------------------9 D. HGF-Met signaling in muscle differentiation and maintenance of rhabdomyosarcoma--11 E. Different splicing variants of Met---------------------------------------------------------------------13 F. D13Met, a novel alternative splicing variant of Met -----------------------------------------15 Ⅱ. MATERIALS AND METHODS-----------------------------------------------------------------17 A. Cell culture and transfections --------------------------------------------------------------------17 B. Reagents and antibodies--------------------------------------------------------------------------------18 C. RT-PCR----------------------------------------------------------------------------------------------------19 D. Immunoprecipitation and Western blotting--------------------------------------------------------19 E. Cell proliferation and thymidine incorporation assay--------------------------------------------20 F. Soft-agar colony formation assay----------------------------------------------------------------------21 G. In vivo tumorigenesis assay----------------------------------------------------------------------------21 H. Colony generation assay--------------------------------------------------------------------------------22 I. Migration assay--------------------------------------------------------------------------------------------22 J. Differentiation induction of primary cell or rhabdomyosarcoma cell lines------------------23 K. Lentiviral vector production------------------------------------------------------------------------------23 L. Statistical analysis------------------------------------------------------------------------------------------24 Ⅲ. RESULTS-------------------------------------------------------------------------------------------25 Part. 1. Inhibition of HGF-Met signaling by 13Met -------------------------------------------25 A. 13Met inhibits Met activation induced by HGF -----------------------------------------------25 B. 13Met inhibits HGF-Met signaling-dependent cell proliferation and colony generation-----------------------------------------------------------------------------------------------------28 C. 13Met inhibits tumor growth in mice-------------------------------------------------------------32 D. Status of HGF-Met signaling is variable in rhabdomyosarcoma cells-----------------------34 E. Met silencing induces inhibition of ERK phosphorylation in RD cells-----------------------36 F. D13Met inhibits HGF-Met signaling in RH18 and RD cells------------------------------------38 G. Δ13Met reduces colony formation in RD cells----------------------------------------------------40 H. Δ13Met inhibits migration of RD cells-------------------------------------------------------------42 Part. 2. Induction of differentiation by D13Met ----------------------------------------------44 I. D13Met is induced during muscle differentiation-------------------------------------------------44 J. Abolishment of D13Met induction with specific siRNA results in delayed differentiation of primary human skeletal muscle cells-------------------------------------------- 48 K. Overexpression of D13Met enhances differentiation in primary human skeletal muscle cells---------------------------------------------------------------------------------------------------------51 L. Δ13Met is unable to induce differentiation of RD cells------------------------------------------54 M. Ectopic expression of D13Met hardly increases MHC expression in several Rhabdo- myosarcoma cell lines under differentiation condition------------------------------------56 Ⅳ. DISCUSSION---------------------------------------------------------------------------------------58 Ⅴ. CONCLUSION-------------------------------------------------------------------------------------63 BIBLIOGRAPHY--------------------------------------------------------------------------------------64 국문요약-------------------------------------------------------------------------------------------------74-
dc.language.isoeng-
dc.publisherThe Graduate School, Ajou University-
dc.rights아주대학교 논문은 저작권에 의해 보호받습니다.-
dc.title새로운 간세포 성장인자 수용체 변이형의 암화 억제 능력-
dc.typeThesis-
dc.contributor.affiliation아주대학교 일반대학원-
dc.contributor.department일반대학원 분자과학기술학과-
dc.date.awarded2009. 8-
dc.description.degreeMaster-
dc.identifier.localId568005-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000010018-
dc.subject.keyword간세포-
dc.subject.keyword성장인자-
dc.subject.keyword수용체-
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Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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