Anhang

Tabelle 4: Liste der mindestens zweifach differentiell exprimierten Gene in den metastatischen gegenüber nicht-metastatischen MTCs („MTC-Liste“)

Gen

Beschreibung

Expressions-veränderung a

E2F- Gen b

Expression verifiziert c

Zellzyklus und DNA-Replikation

Rgc32

Response gene to complement 32

-3.06

Icbp90

Ubiquitin-like, containing PHD and RING finger domains, 1

2.02

x

Cdc7

Cell division cycle 71 homolog (S. cerevisiae)-like 1

2.03

AurB

Serine/threonine kinase 12 (aurora kinase B)

2.04

x

Cdca5

Cell division cycle associated 5

2.07

Ccnb2

Cyclin B2

2.10

x

Cdc20

Cell division cycle 20 homolog (S. cerevisiae)

2.12

x

Ccnb1

Cyclin B1

2.18

x

Skp2

S-phase kinase-associated protein 2 (p45)

2.19

x

Dna2l

DNA2 DNA replication helicase 2-like (yeast)

2.23

x

Pola1

Polymerase (DNA directed), alpha 1

2.27

Cdc2a

Cell division cycle 2 homolog A (S. pombe)

2.27

x

Cdca3

Cell division cycle associated 3

2.33

Cks1

CDC28 protein kinase 1b

2.34

Cks2

CDC28 protein kinase regulatory subunit 2

2.34

x

Pbk

T-LAK cell-originated protein kinase

2.35

x

Rfc4

Replication factor C (activator 1) 4

2.53

Ccna2

Cyclin A2

2.65

x

Brrn1

Barren homolog (Drosophila)

3.25

x

Lek1

Leucine, glutamic acid, lysine family 1 protein

3.44

Dbf4

Activator of S phase kinase

2.03

Mitose/Cytokinese

Spag5

Sperm associated antigen 5

2.01

Ttk

Ttk protein kinase

2.08

Bub1

Budding uninhibited by benzimidazoles 1 homolog (S. cerevisiae)

2.12

x

ja

Racgap1

Rac GTPase-activating protein 1

2.18

ja

Cep55

Centrosomal protein 55 kDa

2.18

ja

Prc1

Protein regulator of cytokinesis 1

2.20

x

ja

Ube2c

Ubiquitin-conjugating enzyme E2C

2.22

Incenp

Inner centromere protein

2.23

Ckap2

Cytoskeleton associated protein 2

2.43

Cdt2

Denticleless homolog

2.56

Ect2

Ect2 oncogene

2.57

x

ja

Plk4

Serine/threonine kinase 18

2.63

Nusap1

Nucleolar and spindle associated protein 1

2.83

Anln

Anillin, actin binding protein

3.00

x

Chromatin

Hist1H2ab

Histone 1, H2ab

2.76

Cenpa

Centromere autoantigen A

2.26

ja

Asf1b

ASF1 anti-silencing function 1 homolog B

2.27

x

Ncapd1

Non-SMC Condensin I complex subunit D

2.06

x

Ncapg

Chromosome condensation protein G

2.04

Ncapg2

Non-SMC Condensin II complex subunit G2

2.48

ja

Smc4l1

SMC4 structural maintenance of chromosomes 4-like 1 (yeast)

2.21

DNA Reparatur

Brca1

Breast cancer 1

2.12

x

Rad51

RAD51 homolog (S. cerevisiae)

2.21

x

RAD51ap1

RAD51 associated protein 1

2.55

x

Kernmetabolismus

Ak3l1

Adenylate kinase 4

2.18

Rrm2

Ribonucleotide reductase M2

3.12

x

Signalwegkomponenten

Tgn

Thyroglobulin

-11.16

Hsp90

Heat shock protein 1

-3.51

Klf9

Kruppel-like factor 9

-2.37

S100a11

S100 calcium binding protein A11 (calizzarin)

-2.26

Socs2

Suppressor of cytokine signaling 2

-2.18

Gcgr

Glucagon receptor

-2.15

Bmyc

Brain expressed myelocytomatosis oncogene

-2.09

Rhoc

Ras homolog gene family, member C

-2.06

nein

Ncstn

Nicastrin

-2.05

Ager

Advanced glycosylation end product-specific receptor

-2.04

Ephexin

Neuronal guanine nucleotide exchange factor

-2.04

Fn14

Tumor necrosis factor receptor superfamily, member 12a

-2.03

ja

Pps

Putative phosphatase

-2.01

Robo1

Roundabout homolog 1 (Drosophila)

2.01

Camkk2

Calcium/calmodulin-dependent protein kinase kinase 2, beta

2.06

Vlgr1

Monogenic, audiogenic seizure susceptibility 1

2.08

Trim25

Tripartite motif protein 25

2.08

Crabp1

Cellular retinoic acid binding protein I

2.12

Pins

Pins homolog (Drosophia)

2.35

ja

Mak

Male germ cell-associated kinase

2.40

c-myb

Myeloblastosis oncogene

2.48

Psrc1

Differential display and activated by p53

2.82

Tal6

Transmembrane 4 superfamily member 1

3.01

Irs1

Insulin receptor substrate 1

3.73

Cytoskelett/Transport

Arl4d

ADP-ribosylation factor 4-like

-2.72

Anxa1

Annexin A1

-2.43

Cldn4

Claudin 4

-2.42

Aqp5

Aquaporin 5

-2.22

Clca4

Chloride channel calcium activated 4

-2.16

Slc25a29

Solute carrier family 25 (mitochondrial carrier, palmitoylcarnitine transporter), member 29

-2.08

Cap1

Adenylyl cyclase-associated CAP protein homolog 1 (S. cerevisiae, S. pombe)

-2.05

Dnm3

Dynamin 3

-2.01

Marcks

Myristoylated alanine rich protein kinase C substrate

2.15

Slc20a1

Solute carrier family 20, member 1

2.43

Cacna1h

Calcium channel, voltage-dependent, T type, alpha 1H subunit

2.70

Kcnmb2

Potassium large conductance calcium-activated channel, subfamily M, beta member 2

3.30

Entzündungen

Lcn2

Lipocalin2

-3.87

Plunc

Palate, lung, and nasal epithelium carcinoma associated

-3.56

Mal

Myelin and lymphocyte protein, T-cell differentiation protein

-2.41

Metabolismus

Cbr2

Carbonyl reductase 2

-2.65

Fuca1

Fucosidase, alpha-L- 1

-2.33

Pitpnc1

Phosphatidylinositol transfer protein, cytoplasmic 1

-2.03

Oxct1

3-oxoacid CoA transferase

2.13

Elovl2

Elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 2

2.27

ChREBP

Williams-Beuren syndrome chromosome region 14 homolog (human)

2.32

Verschiedene

Timp3

Tissue inhibitor of metalloproteinase 3

-2.92

x

Napsa

Kidney-derived aspartic protease-like protein

-2.91

Cy-CAP

Peptidylprolyl isomerase C-associated protein

-2.43

Tcfcp2l1

Tcfcp2-related transcriptional repressor 1

-2.39

Srxn1

Sulfiredoxin 1 homolog (S. Cervisiae)

-2.39

Tinagl

Lipocalin 7

-2.37

Gtl2

Maternally expressed gene 3

-2.26

Efemp2

Epidermal growth factor-containing fibulin-like extracellular matrix protein 2

-2.16

Fkbp11

FK506 binding protein 11

-2.10

Adcy7

Adenylate cyclase 7

2.01

Pvt-1

Plasmacytoma variant translocation 1

2.01

Fignl-1

Fidgetin-like 1

2.06

Depdc7

DEP domain containing 7

2.11

Elavl-3

ELAV (embryonic lethal, abnormal vision, Drosophila)-like 3

2.12

Birc5

Baculoviral IAP repeat-containing 5

2.26

Bim

BCL2-like 11 (apoptosis facilitator)

2.30

Mus musculus beta globin mRNA, partial cds

2.28

Sfpq

Splicing factor proline/glutamine rich (polypyrimidine tract binding protein associated)

2.36

Bicc1

Bicaudal C homolog 1 (Drosophila)

2.36

HCV NS5A-transactivated protein 9 homolog

2.42

Tex15

Testis expressed gene 15

2.63

ja

Six1

Sine oculis-related homeobox 1 homolog (Drosophila)

2.82

Ki-67

Antigen identified by monoclonal antibody Ki 67

2.91

Unbekannt

RIKEN cDNA 1600029D21 gene

-3.40

cDNA sequence BC004044

-2.29

Mus musculus adult male corpora quadrigemina cDNA, RIKEN full-length enriched library, clone:B230312E22 product:hypothetical protein, full insert sequence.

2.01

Mus musculus, Similar to L1 repeat, Tf subfamily, member 30, clone MGC:7372 IMAGE:3487559, mRNA, complete cds

2.07

RIKEN cDNA 3732412D22 gene

2.13

RIKEN cDNA 6430514L14 gene

2.36

Hypothetical protein 6720403H11

2.53

RIKEN cDNA 0610012A05 gene

2.63

a Positives Vorzeichen: Gen hoch reguliert in den metastatischen gegenüber den nicht-metastatischen MTCs

a Negatives Vorzeichen: Gen herunter reguliert in den metastatischen gegenüber den nicht-metastatischen MTCs

b bereits als E2F-Zielgen bekannt

c differentielle Expression mittels qPCR-Analyse in MTCs verifiziert

Tabelle 5 : Liste der mindestens zweifach differentiell exprimierten Gene in den Rb -/-; E2f3 -/- gegenüber Wildtyp-MEFs („WT/DKO-Liste“)

Gen

Beschreibung

Expresssions-veränderung a

E2F-Gen b

Expression verifiziert c

Zellzyklus und DNA-Replikation

Rb1

Retinoblastoma gene

-3.45

Ccnb2

Cyclin B2

2.02

x

p107

retinoblastoma-like 1 (p107)

2.06

x

ja

Tk1

thymidine kinase 1

2.07

x

Topbp1

topoisomerase (DNA) II beta binding protein

2.13

Cks2

CDC28 protein kinase regulatory subunit 2

2.16

PCNA

proliferating cell nuclear antigen

2.3

x

Rif1

Rap1 interacting factor 1 homolog

2.3

Mcm7

minichromosome maintenance deficient 7 (S. cerevisiae)

2.34

x

USP1

ubiquitin specific protease 1

2.38

Pole2

polymerase (DNA directed), epsilon 2 (p59 subunit)

2.46

x

Ezh2

enhancer of zeste homolog 2

2.53

x

ja

Mcm2

minichromosome maintenance deficient 2 mitotin (S. cerevisiae)

2.56

x

Gmnn

geminin

2.73

x

Pola1

polymerase (DNA directed), alpha 1

2.94

x

ICBP90

ubiquitin-like, containing PHD and RING finger domains, 1

3.26

x

Mcm4

minichromosome maintenance deficient 4 homolog (S. cerevisiae)

3.27

x

Prim1

DNA primase, p49 subunit

3.47

Cdt1

retroviral integration site 2

3.49

x

Ccne2

cyclin E2

3.95

x

Mcm6

minichromosome maintenance deficient 6 (MIS5 homolog, S. pombe) (S. cerevisiae)

5.23

x

ja

Mitose/Cytokinese

Cep55

centrosomal protein 55

2.08

ja

CenpA

centromere autoantigen A

2.1

ja

Spbc25

spindle pole body component 25 homolog

2.13

Bub1

budding uninhibited by benzimidazoles 1 homolog (S. cerevisiae)

2.14

x

ja

Ckap2

cytoskeleton associated protein 2

2.15

Prc1

protein regulator of cytokinesis 1

2.17

x

ja

Anln

anillin, actin binding protein (scraps homolog, Drosophila)

2.17

x

Chromatin

Hist2h3c2

histone 2, H3c2

-2.96

Hist1h1c

histone 1, H1c

-2.4

Hist1h2bc

histone 1, H2bc

-2.31

Hist2h2aa1

histone 2, H2aa1

-2.19

H2afz

H2A histone family, member Z

2.01

HMGB2

high mobility group box 2

2.38

Hmgn2

high mobility group nucleosomal binding domain 2

2.28

Slbp

stem-loop binding protein

2.44

Hells

helicase, lymphoid specific

2.85

Dnmt1

DNA methyltransferase (cytosine-5) 1

3.89

x

DNA Reparatur

Ercc6l

excision repair cross-complementing rodent repair deficiency complementation group 6 - like

2.05

UNG

uracil-DNA glycosylase

2.33

MSH6

mutS homolog 6 (E. coli)

3.57

Kernmetabolismus

Cdc8

deoxythymidylate kinase

2.27

DUT

deoxyuridine triphosphatase

2.38

DCK

deoxycytidine kinase

2.9

Signalwegkomponenten

Bmp1

bone morphogenetic protein 1

-2.41

Igfbp2

insulin-like growth factor binding protein 2

-2.21

LPP3

phosphatidic acid phosphatase type 2B

-2.06

Wnk1

protein kinase, lysine deficient 1

2.03

PRL-3

protein tyrosine phosphatase 4a3

2.09

CkIIalpha

casein kinase II, alpha 1 polypeptide

2.09

Foxg1

forkhead box G1

2.11

CD99

CD99 antigen

2.15

x

TNFAIP8 SCC-S2

tumor necrosis factor, alpha-induced protein 8

2.34

FLASH

caspase 8 associated protein 2

2.7

FABP7

fatty acid binding protein 7, brain

2.74

Cytoskelett

LmnB1

lamin B1

2.04

Pkp2

plakophilin 2

2.12

Lap2

thymopoietin

2.46

Stmn1

stathmin 1

3.06

Stress

Nupr1 / P8

nuclear protein 1

-2.48

MT-2

metallothionein 2

-2.08

Metabolismus

B3galnt1

UDP-Gal:betaGlcNAc beta 1,3-galactosyltransferase, polypeptide 3

2.1

Hat1

histidine aminotransferase 1

2.21

Pltp

phospholipid transfer protein

2.29

Extrazellulär

Lcn7

lipocalin 7

-2.28

Mfap5

microfibrillar associated protein 5

-2.09

Matn2

matrilin 2

2.71

Verschiedenes

Penk1

preproenkephalin 1

-3.17

Crabp2

cellular retinoic acid binding protein II

-2.93

Coch

coagulation factor C homolog (Limulus polyphemus)

-2.82

IL1RN

interleukin 1 receptor antagonist

-2.75

ANXA8

annexin A8

-2.51

Gjb2 / connexin26

gap junction membrane channel protein beta 2

-2.43

AQP1

aquaporin

-2.41

Lum

lumican

-2.29

GTL2

GTL2, imprinted maternally expressed untranslated mRNA

-2.28

Slco2a1

solute carrier organic anion transporter family, member 2a1

-2.19

Lgal3

lectin, galactose binding, soluble 3

-2.09

Ifit1

interferon-induced protein with tetratricopeptide repeats 1

2

Gbp2

guanylate nucleotide binding protein 2

2.02

Casp3

caspase 3, apoptosis related cysteine protease

2.04

Sfrs7

splicing factor, arginine/serine-rich 7

2.06

Paics

phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoribosylaminoimidazole, succinocarboxamide synthetase

2.08

Prdx4

peroxiredoxin 4

2.23

Aspn

asporin

2.23

VAPB

vesicle-associated membrane protein, associated protein B and C

2.26

Trim59

tripartite motif-containing 59

2.26

Crip1

cysteine-rich protein 1 (intestinal)

2.29

ARL6Ip6

ADP-ribosylation factor-like 6 interacting protein 6

2.41

tipin

timeless interacting protein

2.41

Morc4

microrchidia 4

2.48

Heph

hephaestin

2.52

Psip1

PC4 and SFRS1 interacting protein 1

2.58

UTY

ubiquitously transcribed tetratricopeptide repeat gene, Y chromosome

2.66

UBE2T

ubiquitin-conjugating enzyme E2T

2.67

Tex15

testis expressed gene 15

2.78

ja

Rps9

ribosomal protein S9

2.81

Lyzs

lysozyme

2.85

Tcf19

transcription factor 19

2.89

CRABP1

cellular retinoic acid binding protein I

2.98

Hsp40

DnaJ (Hsp40) homolog, subfamily C, member 9

3.27

Lzp-s

P lysozyme structural

3.35

Cox6b2

cytochrome c oxidase subunit VIb, testes-specific

3.67

Jarid1d

jumonji, AT rich interactive domain 1D (Rbp2 like)

3.83

Eif2s3y

eukaryotic translation initiation factor 2, subunit 3, structural gene Y-linked

6.99

Ddx3y

DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y-linked

30.67

Unbekannt

Adult male cecum cDNA, RIKEN full-length enriched library, clone:9130009H04 product:unknown EST, full insert sequence

-3.07

RIKEN cDNA 6330406I15 gene

-2.29

L0288G10-3 NIA Mouse Newborn Ovary cDNA Library Mus musculus cDNA clone L0288G10 3', mRNA sequence.

-2.23

BB119177 RIKEN full-length enriched, adult male urinary bladder Mus musculus cDNA clone 9530069H15 3', mRNA sequence.

-2.14

BB160417 RIKEN full-length enriched, 16 days neonate thymus Mus musculus cDNA clone A130053B20 3', mRNA sequence.

2.18

DNA segment, Chr 17, human D6S56E 5

2.5

RIKEN cDNA 2610042L04 gene

2.51

expressed sequence AW413625

2.75

a Positives Vorzeichen: Gen hoch reguliert in Rb-/-; E2f3-/- gegenüber Wildtyp-MEFs

a Negatives Vorzeichen: Gen herunter reguliert in Rb-/-; E2f3-/- gegenüber Wildtyp-MEFs

b bereits als E2F-Zielgen bekannt

c differentielle Expression mittels qPCR-Analyse in MTCs verifiziert


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