The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer:
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| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2015
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | 111 S. Ill., graph. Darst. |
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Datensatz im Suchindex
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| adam_text | THE EMT-TRANSCRIPTION FACTOR ZEB1 AND THE
CO-ACTIVATOR YAP COOPERATE IN AGGRESSIVE TYPES
OF BREAST CANCER
INAUGURAL-DISSERTATION
ZUR ERLANGUNG DES AKADEMISCHEN GRADES DES DOKTORS DER
NATURWISSENSCHAFTEN
(DR. RER. NAT.)
AN DER FAKULTAT FUR BIOLOGIE UND DER FAKULTAT FUR MEDIZIN
DER ALBERT-LUDWIGS-UNIVERSITAT FREIBURG IM BREISGAU
VORGELEGT VON
WALTRAUT LEHMANN
GEBOREN IN TRIER
FREIBURG IM BREISGAU
JANUAR 2015
HTTP://D-NB.INFO/1071606840
TABLE OF CONTENTS
1
I TABLE OF CONTENTS
I TABLE OF CONTENTS 1
II SUMMARY 4
III ZUSAMMENFASSUNG 6
IV INTRODUCTION 8
1 CANCER 8
2 EPITHELIAL-MESENCHYMAL TRANSITION (EMT) 11
3 THE EMT TRANSCRIPTION FACTOR ZEB1 14
4 THE HIPPO SIGNALING PATHWAY 18
4.1 THE CORE KINASE CASCADE IN DROSOPHILA AND MAMMALS 18
4.2 (CANONICAL) UPSTREAM REGULATORY SIGNALS OF YAP/TAZ 20
4.3 OTHER (NON-CANONICAL) UPSTREAM REGULATORS OF YAP/TAZ 22
4.4 CROSS-TALK WITH OTHER SIGNALING PATHWAYS 23
4.5 THE TRANSCRIPTIONAL CO-ACTIVATOR YAP/TAZ 24
4.6 YAP/TAZ AND THE HIPPO PATHWAY IN CANCER 26
5 BREAST CANCER 27
V OBJECTIVES 31
VI RESULTS 32
1 THE EXPRESSION OF YAP TARGET GENES IN CANCER CELL LINES CORRELATES
WITH AND IS
DEPENDENT ON ZEB1 EXPRESSION 32
2 ZEB1 REGULATES YAP TARGET GENES IN BREAST CANCER CELL LINES 35
3 THE REGULATION OF YAP TARGET GENES IS ZEB1-DEPENDENT AND REQUIRES YAP
39
4 ZEB1 DOES NOT AFFECT YAP PHOSPHORYLATION AND SUBCELLULAR LOCALIZATION
42
5 ZEB1 DIRECTLY ACTIVATES YAP TARGET GENES 44
6 DIRECT INTERACTION BETWEEN ZEB1 AND YAP IS MEDIATED BY THE ZINC FINGER
CLUSTERS
OF ZEB1 47
7 ZEB1 AND YAP TARGET GENE EXPRESSION IS ASSOCIATED WITH THE CLAUDIN-LOW
SUBTYPE
OF BREAST CANCER AND CORRELATES WITH POOR CLINICAL OUTCOME 50
VII DISCUSSION 52
VIII MATERIAL 67
1 CELL LINES 67
2 CELL CULTURE MEDIA AND REAGENTS 67
2
TABLE OF CONTENTS
3 TRANSFECTION REAGENTS 68
4 OTHER REAGENTS 68
5 OLIGONUCLEOTIDES 69
5.1 QPCR 69
5.2 CHIP 70
5.3 SIRNAS 70
5.4 PRIMER FOR CLONING : 70
5.5 PRIMER FOR SEQUENCING 71
6 PLASMIDS AND BACMIDS 71
7 ANTIBODIES 71
7.1 PRIMARY ANTIBODIES 71
7.2 SECONDARY ANTIBODIES 72
7.3 OTHER ANTIBODIES 72
8 KITS 72
9 COMMON BUFFERS AND SOLUTIONS 72
9.1 WESTERN BLOT 72
9.2 CHROMATIN IMMUNOPRECIPITATION 73
9.3 CO-LMMUNOPRECIPITATION 73
9.4 HIS-PULLDOWN 74
9.5 DNA GEL ELECTROPHORESIS 74
9.6 BACTERIAL CULTURE 74
9.7 CELL CULTURE 74
9.8 IMMUNOFLUORESCENCE 74
10 SOFTWARE AND DATABASES 75
IX METHODS 76
1 CELL CULTURE 76
2 CLONING 76
3 SIRNA TRANSFECTION 78
4 RNA ISOLATION, CDNA SYNTHESIS AND QUANTITATIVE RT-PCR (QRT-PCR) 79
5 PROTEIN ISOLATION, SDS GEL ELECTROPHORESIS AND WESTERN BLOT ANALYSIS
80
6 IMMUNOFLUORESCENCE 81
7 PROXIMITY LIGATION ASSAY (PLA) 82
8 CO-LMMUNOPRECIPITATION (CO-IP) 82
9 IN VITRO SYNTHESIS OF HIS-YAP AND HA-ZEB1 83
TABLE OF CONTENTS
3
10HIS-PULLDOWN 84
11 CHROMATIN IMMUNOPRECIPITATION (CHIP) 84
12LUCIFERASE REPORTER ASSAY 85
13 DATA ANALYSIS 85
14 STATISTICAL ANALYSIS 87
X REFERENCES 88
XI APPENDIX 108
1 ABBREVIATIONS 108
2 ACKNOWLEDGEMENT 111
|
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| indexdate | 2024-07-10T07:07:53Z |
| institution | BVB |
| language | English |
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| spelling | Lehmann, Waltraut Verfasser (DE-588)1071240056 aut The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer vorgelegt von Waltraut Lehmann 2015 111 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Freiburg i. Br., Univ., Diss., 2015 Brustkrebs (DE-588)4008528-4 gnd rswk-swf Metastase (DE-588)4125915-4 gnd rswk-swf Transkriptionsfaktor (DE-588)4303350-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Brustkrebs (DE-588)4008528-4 s Transkriptionsfaktor (DE-588)4303350-7 s Metastase (DE-588)4125915-4 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028139568&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Lehmann, Waltraut The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer Brustkrebs (DE-588)4008528-4 gnd Metastase (DE-588)4125915-4 gnd Transkriptionsfaktor (DE-588)4303350-7 gnd |
| subject_GND | (DE-588)4008528-4 (DE-588)4125915-4 (DE-588)4303350-7 (DE-588)4113937-9 |
| title | The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer |
| title_auth | The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer |
| title_exact_search | The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer |
| title_full | The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer vorgelegt von Waltraut Lehmann |
| title_fullStr | The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer vorgelegt von Waltraut Lehmann |
| title_full_unstemmed | The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer vorgelegt von Waltraut Lehmann |
| title_short | The EMT-transcription factor ZEB1 and the co-activator YAP cooperate in aggressive types of breast cancer |
| title_sort | the emt transcription factor zeb1 and the co activator yap cooperate in aggressive types of breast cancer |
| topic | Brustkrebs (DE-588)4008528-4 gnd Metastase (DE-588)4125915-4 gnd Transkriptionsfaktor (DE-588)4303350-7 gnd |
| topic_facet | Brustkrebs Metastase Transkriptionsfaktor Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028139568&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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