Melanoma maintenance by the AP1 transcription factor FOSL1: = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Würzburg
2016
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| Schlagworte: | |
| Online-Zugang: | Volltext Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | veröffentlicht 2017 |
| Beschreibung: | 86 Blätter Illustrationen, Diagramme 30 cm |
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MARC
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| 245 | 1 | 0 | |a Melanoma maintenance by the AP1 transcription factor FOSL1 |b = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom |c vorgelegt von Katja Maurus |
| 246 | 1 | 1 | |a Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom |
| 264 | 1 | |a Würzburg |c 2016 | |
| 300 | |a 86 Blätter |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a veröffentlicht 2017 | ||
| 502 | |b Dissertation |c Julius-Maximilians-Universität Würzburg |d 2016 | ||
| 546 | |a Zusammenfassung in deutscher und englischer Sprache | ||
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Datensatz im Suchindex
| _version_ | 1804177774068367360 |
|---|---|
| adam_text | M ELANOM A MAINTENANCE BY THE A P I
TRANSCRIPTION FACTOR FOSL1
DISSERTATION ZUR ERLANGUNG DES
NATURWISSENSCHAFTLICHEN DOKTORGRADES
DER J U LI US-MAXI MILIANS-U NIVERSITAET WUERZBURG
VORGELEGT VON
KATJA MAURUS
GEBOREN IN M EM M INGEN
WUERZBURG 2016
CONTENT
SUM M
ARY...................................................................................................................................1
ZUSAMMENFASSSUNG...............................................................................................................
2
1
1NTRODUCTION.........................................................................................................................4
1.1 MALIGNANT
MELANOMA.............................................................................................................................
4
1.1.1 OCCURRENCE AND INCIDENCE OF
MELANOMA......................................................................................
4
1.1.2 MELANOCYTE FUNCTION AND MELANOMA
DEVELOPMENT....................................................................4
1.2 MELANOMA PATHOGENESIS AND EFFECTOR
PATHWAYS................................................................................6
1.2.1 FAMILIAL
MELANOMA..........................................................................................................................6
1.2.2 SPORADIC
MELANOMA.........................................................................................................................7
1.2.3 THE
ERKL/2-PATHWAY......................................................................................................................
7
1.2.4 THE
PI3K/AKT-PATHWAY...................................................................................................................
9
1.2.5 THE
MDM/P53-PATHWAY...............................................................................................................
11
1.3 THE API COMPLEX AND ITS COMPONENT FOSL1
.....................................................................................
12
1.3.1 FOSL1- THE FOS-RELATED ANTIGEN 1
...............................................................................................
13
1.3.2 FOSL1 AND ITS BIOLOGICAL
FUNCTION.............................................. 13
1.3.3 TUMORIGENIC FEATURES OF
FOSL1...................................................................................................
14
1.4 AIM OF THE
THESIS...................................................................................................................................
16
2. M ATERIAL AND M
ETHODS...................................................................................................
17
2.1
MATERIAL...............................................................................................................................................17
2.1.1 CELL
LINES..........................................................................................................................................17
2.1.2
PLASMIDS..........................................................................................................................................17
2.1.3 INHIBITORS AND COMPOUNDS
...........................
17
2.1.4
SIRNAS.............................................................................................................................................
18
2.1.5
ANTIBODIES.......................................................................................................................................18
2.1.6
KITS..................................................................................................................................................
19
2.1.7 BUFFERS
19
2.1.8 QPCR
OLIGONUCLEOTIDES..................................................................................................................
20
2.1.9 CLONING
OLIGONUCLEOTIDES..............................................................................................................
20
2.1.10 CHIP
OLIGONUCLEOTIDES.................................................................................................................
20
2.1.11 CHIP
BUFFERS.................................................................................................................................
20
2.1.12 TECHNICAL
EQUIPMENT..................................................................................................................
21
2.2
METHODS..............................................................................................................................................22
2.2.1 CELL CULTURE
METHODS....................................................................................................................
22
2.2.1.1 MAINTENANCE OF
CELLS.............................................................................................................22
2.2.1.2 GENERATION OF TRANSGENIC CELL
LINES......................................................................................
22
2.2.1.3 SIRNA
TRANSFECTION.................................................................................................................
22
2.2.1.4 PROLIFERATION ASSAY
.......................................................................
23
2.2.1.5 TRANSWELL MIGRATION
ASSAY....................................................................................................
23
2.2.1.6 COLONY FORMATION
ASSAY........................................................................................................
23
2.2.1.7 SOFT AGAR
ASSAY.......................................................................................................................
24
2.2.1.8 FACS/ CELL CYCLE
ANALYSIS.......................................................................................................
24
2.2.2 RNA AND DNA
METHODS................................................................................................................24
2.2.2.1 VECTOR CLONING
PROCEDURE.....................................................................................................
24
2.2 2.2 RNA EXTRACTION, CDNA SYNTHESIS AND RT-QPCR
................................................................
25
2.2.3 PROTEIN
METHODS............................................................................................................................26
2.2.3.1 PROTEIN LYSIS, SDS-PAGE AND WESTERN BLOT
..............................
.
........................................
26
2.2.3 2 CHROMATIN IMMUNOPRECIPITATION
(CHIP)...........................................................................27
3
RESULTS.................................................................................................................................
29
3.1 FOSL1 REGULATION IN
MELANOMA...........................................................................................................29
3.1.1 P-ERK1/2- DEPENDENT REGULATION OF
FOSL1................................................................
.
..............29
3.1.2 PI3K- SIGNALING- DEPENDENT REGULATION OF
FOSL1.......................................................................
30
3.1.3 P53- DEPENDENT REGULATION OF FOSL1
.........................................................................................
31
3.2 FOSL1 MEDIATED PRO-TUMORIGENIC EFFECTS IN HUMAN
MELANOMA..................................................... 35
3.2.1 EFFECTS OF FOSL1 ON PROLIFERATION.
37
3.2.2 EFFECTS OF FOSL1 ON
MIGRATION....................................................................................................
37
3.2.3 EFFECTS OF FOSL1 ON COLONY FORMATION AND ANCHORAGE INDEPENDENT
GROWTH
........................
38
3.3 DOWNSTREAM EFFECTORS OF FOSL1 IN
MELANOMA.................................................................................40
3.3.1 MICROARRAY
ANALYSIS......................................................................................................................
40
3.3.2 FOSL1- DEPENDENT REGULATION OF NEURONAL
GENES....................................................................41
3.3.3 EXPRESSION OF NEURONAL TARGET GENES IN MELANOMA CELLS WITH
DIFFERENT DIFFERENTIATION STATES
43
3.3.4 TRANSCRIPTIONAL REGULATORS DOWNSTREAM OF
FOSL1....................................................................45
3.3.5 FOSLL-CHLP ANALYSIS OF THE HMGA1 GENOMIC
REGION................................................................47
3.4 HMGA1 AND ITS ROLE IN
MELANOMA.....................................................................................................
49
3.4.1 HMGA1 REGULATION IN
MELANOMA.................................................................................................49
3.4.2 THE INFLUENCE OF HMGA1 ON NEURONAL GENES
...........................................................................
50
3.4.3 FUNCTIONAL EFFECTS OF HMGA1 IN MELANOMA
.............................................................................
51
3.4.4 HMGA1 AS MEDIATOR OF FOSLL-DRIVEN PRO-TUMORIGENIC EFFECTS
.............................................
52
4.
DISCUSSION.........................................................................................................................55
4.1 FOSLL AND CELLULAR
PLASTICITY................................................................................................................55
4.1.1. FOSLL AS PRO-TUMORIGENIC AND TUMOR-MAINTAINING TRANSCRIPTION
FACTOR
..............................
55
4.1.2 FOSLL AND DEDIFFERENTIATION IN
MELANOMA.............................................................................
55
4.2 HMGA1- A NOVEL PLAYER IN
MELANOMA?...............................................................................................57
4.2.1 TUMOR PROMOTING EFFECTS OF
HMGA1.........................................................................................
58
4.2.2 THE FOSL1/HMGA1 SIGNALING AXIS IN CUTANEOUS
MELANOMA..................................................... 61
4.3
CONCLUSION.............................................................................................................................................63
APPENDIX................................................................................................................................64
1. FOSLL AND
JUN IN THE MITF:XMRK MEDAKA MELANOMA
MODEL................................................................64
2. DOMINANT-NEGATIVE FOSL1 AND JUN IN HUMAN MELANOMA
..................................................
67
BIBLIOGRAPHY..........................................................................................................................
70
PUBLICATIONS.....................................................................
85
ACKNOWLEDGEMENTS
86
|
| any_adam_object | 1 |
| author | Maurus, Katja Maria 19XX- |
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| author_role | aut |
| author_sort | Maurus, Katja Maria 19XX- |
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| building | Verbundindex |
| bvnumber | BV044455140 |
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| spelling | Maurus, Katja Maria 19XX- Verfasser (DE-588)1138591912 aut Melanoma maintenance by the AP1 transcription factor FOSL1 = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom vorgelegt von Katja Maurus Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom Würzburg 2016 86 Blätter Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier veröffentlicht 2017 Dissertation Julius-Maximilians-Universität Würzburg 2016 Zusammenfassung in deutscher und englischer Sprache Melanom (DE-588)4074707-4 gnd rswk-swf Transkriptionsfaktor (DE-588)4303350-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Melanom (DE-588)4074707-4 s Transkriptionsfaktor (DE-588)4303350-7 s DE-604 Erscheint auch als Online-Ausgabe, PDF urn:nbn:de:bvb:20-opus-142995 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-142995 Resolving-System kostenfrei Volltext B:DE-101 application/pdf http://d-nb.info/1137402997/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029855949&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Maurus, Katja Maria 19XX- Melanoma maintenance by the AP1 transcription factor FOSL1 = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom Melanom (DE-588)4074707-4 gnd Transkriptionsfaktor (DE-588)4303350-7 gnd |
| subject_GND | (DE-588)4074707-4 (DE-588)4303350-7 (DE-588)4113937-9 |
| title | Melanoma maintenance by the AP1 transcription factor FOSL1 = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom |
| title_alt | Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom |
| title_auth | Melanoma maintenance by the AP1 transcription factor FOSL1 = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom |
| title_exact_search | Melanoma maintenance by the AP1 transcription factor FOSL1 = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom |
| title_full | Melanoma maintenance by the AP1 transcription factor FOSL1 = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom vorgelegt von Katja Maurus |
| title_fullStr | Melanoma maintenance by the AP1 transcription factor FOSL1 = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom vorgelegt von Katja Maurus |
| title_full_unstemmed | Melanoma maintenance by the AP1 transcription factor FOSL1 = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom vorgelegt von Katja Maurus |
| title_short | Melanoma maintenance by the AP1 transcription factor FOSL1 |
| title_sort | melanoma maintenance by the ap1 transcription factor fosl1 der einfluss des transkriptionsfaktors fosl1 auf protumorigene effekte im melanom |
| title_sub | = Der Einfluss des Transkriptionsfaktors FOSL1 auf protumorigene Effekte im Melanom |
| topic | Melanom (DE-588)4074707-4 gnd Transkriptionsfaktor (DE-588)4303350-7 gnd |
| topic_facet | Melanom Transkriptionsfaktor Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-142995 http://d-nb.info/1137402997/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029855949&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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