Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Freiburg im Breisgau
Oktober 2022
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | Enthält 1 Sonderabdruck |
| Beschreibung: | XVI, 90 Seiten, Seite A-D, 23 Seiten Illustrationen, Diagramme 30 cm |
Internformat
MARC
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| 100 | 1 | |a Heß, Lisa |d 1993- |e Verfasser |0 (DE-588)1277179883 |4 aut | |
| 245 | 1 | 0 | |a Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation |c vorgelegt von Lisa Heß, geborene Lehmann |
| 264 | 1 | |a Freiburg im Breisgau |c Oktober 2022 | |
| 300 | |a XVI, 90 Seiten, Seite A-D, 23 Seiten |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Enthält 1 Sonderabdruck | ||
| 502 | |b Dissertation |c Albert-Ludwigs-Universität Freiburg |d 2022 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u https://d-nb.info/1280435151/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034182185&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-034182185 | ||
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| 883 | 2 | |8 3\p |a dnb |d 20230310 |q DE-101 |u https://d-nb.info/provenance/plan#dnb | |
Datensatz im Suchindex
| _version_ | 1804185095804813312 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
ZUSAMMENFASSUNG
.................................................................................................................
I
ABSTRACT
...................................................................................................................................
III
TABLE
OF
CONTENTS
.....................................................................................................................
V
LIST
OF
FIGURES
........................................................................................................................
VIII
LIST
OF
TABLES
............................................................................................................................
X
ABBREVIATIONS
.........................................................................................................................
XI
1
INTRODUCTION
.......................................................................................................................
1
1.1
DIPEPTIDYL-PEPTIDASE
IV
FAMILY
OF
PROTEASES
...............................................................
1
1.2
BREAST
CANCER
............................................................................................................
3
1.3
BRAIN
DEVELOPMENT
AND
NEURODEGENERATION
..............................................................
6
2
AIMS
AND
OBJECTIVES
........................................................................................................
10
3
MATERIALS
AND
METHODS
...................................................................................................
11
3.1
MATERIALS
AND
CHEMICALS
..........................................................................................
11
3.1.1
CHEMICALS
AND
REAGENTS
....................................................................................
11
3.1.2
CONSUMABLES
AND
EQUIPMENT
............................................................................
15
3.1.3
BUFFERS,
SOLUTIONS,
AND
MEDIA
............................................................................
16
3.2
MOUSE
MODELS
AND
GENOTYPING
................................................................................
17
3.2.1
APPROVALS
..........................................................................................................
17
3.2.2
MOUSE
LINES
.......................................................................................................
17
3.2.3
ODOR
AVOIDANCE
TEST
..........................................................................................
18
3.2.4
GENOTYPING
OF
MICE
...........................................................................................
18
3.2.5
DROPLET
DIGITALYY
POLYMERASE
CHAIN
REACTION
.....................................................
19
3.2.6
PREPARATION
OF
MICE
AND
HISTOLOGY
....................................................................
20
3.2.7
IMMUNOHISTOCHEMISTRY
AND
IMMUNOFLUORESCENCE
.............................................
20
3.2.8
CARMINE
ALUM
STAINING
......................................................................................
21
3.3
MOLECULAR
CELL
BIOLOGY
AND
BIOCHEMISTRY
.................................................................
21
3.3.1
CELL
LINES
...........................................................................................................
21
V
TABLE
OF
CONTENTS
3.3.2
CELL
COUNTING
.....................................................................................................
23
3.3.3
QUANTITATIVE
REAL-TIME
REVERSE
TRANSCRIPTASE
POLYMERASE
CHAIN
REACTION
..........
23
3.3.4
PROTEIN
QUANTIFICATION
.........................................................................................
24
3.3.5
WESTERN
BLOT
.....................................................................................................
24
3.3.6
DIPEPTIDYL
PEPTIDASE
ACTIVITY
ASSAY
...................................................................
26
3.3.7
IMMUNOFLUORESCENCE
OF
2D
CULTURE
...................................................................
27
3.3.8
IMMUNOFLUORESCENCE
OF
3D
CULTURE
...................................................................
27
3.3.9
ANNEXIN
V-BINDING
ASSAY
..................................................................................
28
3.3.10
GAP
CLOSURE
ASSAY
............................................................................................
28
3.3.11
LYSOTRACKER
ASSAY
.............................................................................................
28
3.3.12
INVASION
ASSAY
..................................................................................................
29
3.4
STATISTICS
...................................................................................................................
29
3.4.1
TCGA
PATIENT
DATA
RETRIEVAL
AND
ANALYSIS
.........................................................
29
3.4.2
DATA
PRESENTATION
AND
STATISTICS
........................................................................
30
4
RESULTS
............................................................................................................................
31
4.1
STAGE-DEPENDENT FUNCTIONS
OF
DPP9
IN
MAMMARY
CANCER
PROGRESSION
..................
31
4.1.1
LOW
DPP9
MRNA
EXPRESSION
CORRELATES
WITH
POOR
OVERALL
SURVIVAL
OF
BREAST
CANCER
PATIENTS
...............................................................................................................
31
4.1.2
DPP9
DEFICIENCY
DELAYED
TUMOR
ONSET
BUT
ENHANCES
METASTASES
COUNT
IN
MMTV
PYMT
MICE
......................................................................................................................
34
4.1.3
DPP9
DEFICIENCY
STALLED
TUMORIGENIC
TRANSFORMATION
AND
PROMOTES
TGF-SS1
INDUCED
EMT
OF
MCF10ATET
KRAS
G12V
SPHEROIDS
..........................................................
40
4.1.4
DPP9
DEFICIENCY
PROMOTES
MIGRATION
AND
INVASION
OF
MURINE
PRIMARY
BREAST
TUMOR
CELLS
BY
STABILIZATION
OF
ZEB1
................................................................................
45
4.2
DPP9
IN
NEURONAL
DIFFERENTIATION
..............................................................................
49
4.2.1
HOMOZYGOUS
DPP9
DEFICIENCY
REDUCES
BODY
AND
BRAIN
WEIGHT
BUT
INCREASES
ODOR
AVOIDANCE
OF
MICE
.........................................................................................................
49
4.2.2
DPP8/9
INHIBITION
INCREASES
SENSITIVITY
TO
THE
SENOLYTIC
AGENT
NAVITOCLAX
IN
LUHMES
CELLS
...............................................................................................................
52
4.2.3
DPP8/9
INHIBITION
BLOCKS
AUTOPHAGIC
FLUX
IN
LUHMES
CELLS
..............................
54
VI
TABLE
OF
CONTENTS
5
DISCUSSION
.......................................................................................................................
60
5.1
STAGE-DEPENDENT FUNCTIONS
OF
DPP9
IN
MAMMARY
CANCER
PROGRESSION
...................
60
5.1.1
DPP9
DEFICIENCY
DURING
TUMOR
INITIATION
DELAYS
BREAST
TUMOR
ONSET
.................
60
5.1.2
DPP9
DEFICIENCY
ENHANCES
METASTATIC
SPREAD
OF
BREAST
TUMOR
CELLS
...............
64
5.2
DPP9
IN
NEURONAL
DIFFERENTIATION
..............................................................................
68
5.2.1
HOMOZYGOUS
DPP9
DEFICIENCY
IN
VIVO
AND
DPP8/9
INHIBITION
IN
VITRO
INCREASED
CELL
DEATH
OF
NEURONS
......................................................................................................
68
5.2.2
INHIBITION
OF
DPP8/9
IN
THE
LUHMES
CELL
LINE
IMPAIRS
AUTOPHAGIC
LYSOSOME
REFORMATION
......................................................................................................................
72
6
REFERENCES
.......................................................................................................................
76
7
ACKNOWLEDGEMENT
(DANKSAGUNG)
...................................................................................
89
8
APPENDIX
...........................................................................................................................
A
8.1
CURRICULUM
VITAE
.........................................................................................................
A
8.1
SUPERVISION
OF
THESIS
..................................................................................................
B
8.2
ATTENDED
CONFERENCES
................................................................................................
B
8.3
ATTENDED
COURSES
.......................................................................................................
B
8.4
LIST
OF
PUBLICATIONS
.....................................................................................................
C
8.5
DECLARATION
(ERKLAERUNG)
.............................................................................................
D
VII
|
| adam_txt |
TABLE
OF
CONTENTS
ZUSAMMENFASSUNG
.
I
ABSTRACT
.
III
TABLE
OF
CONTENTS
.
V
LIST
OF
FIGURES
.
VIII
LIST
OF
TABLES
.
X
ABBREVIATIONS
.
XI
1
INTRODUCTION
.
1
1.1
DIPEPTIDYL-PEPTIDASE
IV
FAMILY
OF
PROTEASES
.
1
1.2
BREAST
CANCER
.
3
1.3
BRAIN
DEVELOPMENT
AND
NEURODEGENERATION
.
6
2
AIMS
AND
OBJECTIVES
.
10
3
MATERIALS
AND
METHODS
.
11
3.1
MATERIALS
AND
CHEMICALS
.
11
3.1.1
CHEMICALS
AND
REAGENTS
.
11
3.1.2
CONSUMABLES
AND
EQUIPMENT
.
15
3.1.3
BUFFERS,
SOLUTIONS,
AND
MEDIA
.
16
3.2
MOUSE
MODELS
AND
GENOTYPING
.
17
3.2.1
APPROVALS
.
17
3.2.2
MOUSE
LINES
.
17
3.2.3
ODOR
AVOIDANCE
TEST
.
18
3.2.4
GENOTYPING
OF
MICE
.
18
3.2.5
DROPLET
DIGITALYY
POLYMERASE
CHAIN
REACTION
.
19
3.2.6
PREPARATION
OF
MICE
AND
HISTOLOGY
.
20
3.2.7
IMMUNOHISTOCHEMISTRY
AND
IMMUNOFLUORESCENCE
.
20
3.2.8
CARMINE
ALUM
STAINING
.
21
3.3
MOLECULAR
CELL
BIOLOGY
AND
BIOCHEMISTRY
.
21
3.3.1
CELL
LINES
.
21
V
TABLE
OF
CONTENTS
3.3.2
CELL
COUNTING
.
23
3.3.3
QUANTITATIVE
REAL-TIME
REVERSE
TRANSCRIPTASE
POLYMERASE
CHAIN
REACTION
.
23
3.3.4
PROTEIN
QUANTIFICATION
.
24
3.3.5
WESTERN
BLOT
.
24
3.3.6
DIPEPTIDYL
PEPTIDASE
ACTIVITY
ASSAY
.
26
3.3.7
IMMUNOFLUORESCENCE
OF
2D
CULTURE
.
27
3.3.8
IMMUNOFLUORESCENCE
OF
3D
CULTURE
.
27
3.3.9
ANNEXIN
V-BINDING
ASSAY
.
28
3.3.10
GAP
CLOSURE
ASSAY
.
28
3.3.11
LYSOTRACKER
ASSAY
.
28
3.3.12
INVASION
ASSAY
.
29
3.4
STATISTICS
.
29
3.4.1
TCGA
PATIENT
DATA
RETRIEVAL
AND
ANALYSIS
.
29
3.4.2
DATA
PRESENTATION
AND
STATISTICS
.
30
4
RESULTS
.
31
4.1
STAGE-DEPENDENT FUNCTIONS
OF
DPP9
IN
MAMMARY
CANCER
PROGRESSION
.
31
4.1.1
LOW
DPP9
MRNA
EXPRESSION
CORRELATES
WITH
POOR
OVERALL
SURVIVAL
OF
BREAST
CANCER
PATIENTS
.
31
4.1.2
DPP9
DEFICIENCY
DELAYED
TUMOR
ONSET
BUT
ENHANCES
METASTASES
COUNT
IN
MMTV
PYMT
MICE
.
34
4.1.3
DPP9
DEFICIENCY
STALLED
TUMORIGENIC
TRANSFORMATION
AND
PROMOTES
TGF-SS1
INDUCED
EMT
OF
MCF10ATET
KRAS
G12V
SPHEROIDS
.
40
4.1.4
DPP9
DEFICIENCY
PROMOTES
MIGRATION
AND
INVASION
OF
MURINE
PRIMARY
BREAST
TUMOR
CELLS
BY
STABILIZATION
OF
ZEB1
.
45
4.2
DPP9
IN
NEURONAL
DIFFERENTIATION
.
49
4.2.1
HOMOZYGOUS
DPP9
DEFICIENCY
REDUCES
BODY
AND
BRAIN
WEIGHT
BUT
INCREASES
ODOR
AVOIDANCE
OF
MICE
.
49
4.2.2
DPP8/9
INHIBITION
INCREASES
SENSITIVITY
TO
THE
SENOLYTIC
AGENT
NAVITOCLAX
IN
LUHMES
CELLS
.
52
4.2.3
DPP8/9
INHIBITION
BLOCKS
AUTOPHAGIC
FLUX
IN
LUHMES
CELLS
.
54
VI
TABLE
OF
CONTENTS
5
DISCUSSION
.
60
5.1
STAGE-DEPENDENT FUNCTIONS
OF
DPP9
IN
MAMMARY
CANCER
PROGRESSION
.
60
5.1.1
DPP9
DEFICIENCY
DURING
TUMOR
INITIATION
DELAYS
BREAST
TUMOR
ONSET
.
60
5.1.2
DPP9
DEFICIENCY
ENHANCES
METASTATIC
SPREAD
OF
BREAST
TUMOR
CELLS
.
64
5.2
DPP9
IN
NEURONAL
DIFFERENTIATION
.
68
5.2.1
HOMOZYGOUS
DPP9
DEFICIENCY
IN
VIVO
AND
DPP8/9
INHIBITION
IN
VITRO
INCREASED
CELL
DEATH
OF
NEURONS
.
68
5.2.2
INHIBITION
OF
DPP8/9
IN
THE
LUHMES
CELL
LINE
IMPAIRS
AUTOPHAGIC
LYSOSOME
REFORMATION
.
72
6
REFERENCES
.
76
7
ACKNOWLEDGEMENT
(DANKSAGUNG)
.
89
8
APPENDIX
.
A
8.1
CURRICULUM
VITAE
.
A
8.1
SUPERVISION
OF
THESIS
.
B
8.2
ATTENDED
CONFERENCES
.
B
8.3
ATTENDED
COURSES
.
B
8.4
LIST
OF
PUBLICATIONS
.
C
8.5
DECLARATION
(ERKLAERUNG)
.
D
VII |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author | Heß, Lisa 1993- |
| author_GND | (DE-588)1277179883 |
| author_facet | Heß, Lisa 1993- |
| author_role | aut |
| author_sort | Heß, Lisa 1993- |
| author_variant | l h lh |
| building | Verbundindex |
| bvnumber | BV048918090 |
| ctrlnum | (OCoLC)1356796566 (DE-599)DNB1280435151 |
| discipline | Medizin |
| discipline_str_mv | Medizin |
| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV048918090 |
| illustrated | Illustrated |
| index_date | 2024-07-03T21:55:09Z |
| indexdate | 2024-07-10T09:49:47Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-034182185 |
| oclc_num | 1356796566 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | XVI, 90 Seiten, Seite A-D, 23 Seiten Illustrationen, Diagramme 30 cm |
| publishDate | 2022 |
| publishDateSearch | 2022 |
| publishDateSort | 2022 |
| record_format | marc |
| spelling | Heß, Lisa 1993- Verfasser (DE-588)1277179883 aut Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation vorgelegt von Lisa Heß, geborene Lehmann Freiburg im Breisgau Oktober 2022 XVI, 90 Seiten, Seite A-D, 23 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Enthält 1 Sonderabdruck Dissertation Albert-Ludwigs-Universität Freiburg 2022 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1280435151/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034182185&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p emakn 0,30001 20230214 DE-101 https://d-nb.info/provenance/plan#emakn 2\p dnb 20230310 DE-101 https://d-nb.info/provenance/plan#dnb 3\p dnb 20230310 DE-101 https://d-nb.info/provenance/plan#dnb |
| spellingShingle | Heß, Lisa 1993- Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation |
| subject_GND | (DE-588)4113937-9 |
| title | Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation |
| title_auth | Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation |
| title_exact_search | Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation |
| title_exact_search_txtP | Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation |
| title_full | Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation vorgelegt von Lisa Heß, geborene Lehmann |
| title_fullStr | Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation vorgelegt von Lisa Heß, geborene Lehmann |
| title_full_unstemmed | Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation vorgelegt von Lisa Heß, geborene Lehmann |
| title_short | Stage-dependent functions of dipeptidyl-peptidase 9 in mammary cancer progression and neuronal differentiation |
| title_sort | stage dependent functions of dipeptidyl peptidase 9 in mammary cancer progression and neuronal differentiation |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1280435151/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034182185&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT heßlisa stagedependentfunctionsofdipeptidylpeptidase9inmammarycancerprogressionandneuronaldifferentiation |
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