Table 1

Up-regulation and down-regulation of gene expression by APC

Gene*Official gene namePathway affectedReference sequenceOther protein nameSources
Up-regulation      
    BCL2A1 BCL2-related protein A1 Apoptosis NM_004049 A1 Joyce et al,15  Riewald and Ruf30  
    BMP2 Bone morphogenetic protein 2 Differentiation NM_001200 BMP-2 Riewald et al,19  Riewald and Ruf30  
    CCL2 Chemokine (C-C motif) ligand 2 Inflammation NM_002982 MCP-1 Riewald et al,19  Franscini et al33  
    CX3CL1† Chemokine (C-X3-C motif) ligand 1 Adhesion NM_002996 Fractalkine Joyce et al,15  Franscini et al,33  Brueckmann et al34  
    CXCL2 Chemokine (C-X-C motif) ligand 2 Inflammation NM_002089 MIP-2, GRO Riewald et al,19  Riewald and Ruf,30  Franscini et al33  
    DDX21 DEAD (Asp-Glu-Ala-Asp) box polypeptide 21 Transcription NM_004728 RNA helicase II/Gu-α Joyce et al15  
    F3 Coagulation factor III (thromboplastin, tissue factor) Coagulation NM_001993 TF, CD142 Riewald et al,19  Riewald and Ruf30  
    HBEGF Heparin-binding EGF-like growth factor Proliferation NM_001945 HBEGF Riewald et al19  
    IL1RI† Interleukin 1 receptor, type 1 Inflammation NM_000877 IL-1R1, CD121a Riewald and Ruf,30  Franscini et al33  
    IL6 Interleukin 6 (interferon, beta 2) Inflammation NM_000600 IL-6 Franscini et al,33  Hooper et al35  
    IL8 Interleukin 8 Inflammation NM_000584 IL-8, CXCL-8 Franscini et al,33  Hooper et al,35  Brueckmann et al36  
    NFKB1† Nuclear factor of kappa light polypeptide gene enhancer 1 Transcription NM_003998 NF-κB Joyce et al,15  Joyce and Grinnell,32  Franscini et al33  
    NFKB2† Nuclear factor of kappa light polypeptide gene enhancer 2 Transcription NM_002502 NF-κB2 p100 Joyce et al,15  Riewald and Ruf,30  Franscini et al33  
    NOS3 Nitric oxide synthase 3 (endothelial cell) Inflammation NM_000603 eNOS Joyce et al15  
    NR4A1 Nuclear receptor subfamily 4, group A, member 1 Apoptosis NM_173157 TR3, Nur77, NA4A1 Riewald et al,19  Riewald and Ruf,30  Franscini et al33  
    NR4A2 Nuclear receptor subfamily 4, group A, member 2 Transcription NM_006186 NURR1, NA4A2 Riewald et al,19  Riewald and Ruf30  
    NR4A3 Nuclear receptor subfamily 4, group A, member 3 Transcription NM_006981 NOR-1, NA4A3 Riewald et al,19  Riewald and Ruf30  
    PCNA Proliferating cell nuclear antigen Cell cycle NM_002592 PCNA Joyce et al15  
    PTGS2 Prostaglandin-endoperoxide synthase 2 Inflammation NM_000963 COX-2 Riewald et al,19  Riewald and Ruf,30  Brueckmann et al37  
    SMAD3 SMAD, mothers against DPP homolog 3 (Drosophila) Apoptosis NM_005902 SMAD-3 Joyce et al15  
    TNFAIP3 Tumor necrosis factor, alpha-induced protein 3 Apoptosis NM_006290 A20 Joyce et al,15  Riewald et al19  
Down-regulation      
    B2M Beta-2-microglobulin Inflammation NM_004048 B2M Joyce and Grinnell32  
    BIRC5 Baculoviral IAP repeat-containing 5 (survivin) Apoptosis NM_001168 Survivin Joyce and Grinnell,32  Franscini et al33  
    CALR Calreticulin Inflammation NM_004343 Ro, cC1qR Joyce et al,15  Joyce and Grinnell32  
    CMKOR1 Chemokine orphan receptor 1 Cell signaling NM_020311 RDC1 Joyce et al15  
    CX3CL1† Chemokine (C-X3-C motif) ligand 1 Adhesion NM_002996 Fractalkine Joyce et al,15  Franscini et al,33  Brueckmann et al34  
    EFNA1 Ephrin-A1 Chemoattract NM_004428 Ephrin-A1 Joyce et al15  
    ICAM1 Intercellular adhesion molecule 1 (CD54) Adhesion NM_000201 ICAM-1, CD54 Joyce et al,15  Franscini et al33  
    IL1R1† Interleukin 1 receptor, type I Inflammation NM_000877 IL-1R1, CD121a Riewald and Ruf,30  Franscini et al33  
    LTB Lymphotoxin beta (TNF superfamily, member 3) Inflammation NM_002341 LT-β Joyce and Grinnell32  
    MMP10 Matrix metallopeptidase 10 (stromelysin 2) Proteolysis NM_002425 MMP-10 Joyce et al15  
    NFKB1† Nuclear factor of kappa light polypeptide gene enhancer 1 Transcription NM_003998 NF-κB Joyce et al,15  Joyce and Grinnell,32  Franscini et al33  
    NFKB2† Nuclear factor of kappa light polypeptide gene enhancer 2 Transcription NM_002502 NF-κB2 p100 Joyce et al,15  Riewald and Ruf30  
    SELE Selectin E (endothelial adhesion molecule 1) Adhesion NM_000450 E-selectin, CD62E Joyce et al,15  Franscini et al33  
    SOD2 Superoxide dismutase 2, mitochondrial Oxidation NM_000636 MnSOD Joyce et al15  
    THBS1‡ Thrombospondin 1 Adhesion NM_003246 TSP-1 Riewald and Ruf30  
    TP53‡ Tumor protein p53 (Li-Fraumeni syndrome) Apoptosis NM_000546 p53 Cheng et al,16  Riewald and Ruf,30  Guo et al31  
    VCAM1 Vascular cell adhesion molecule 1 Adhesion NM_080682 VCAM-1, CD106 Joyce et al,15  Franscini et al33  
Gene*Official gene namePathway affectedReference sequenceOther protein nameSources
Up-regulation      
    BCL2A1 BCL2-related protein A1 Apoptosis NM_004049 A1 Joyce et al,15  Riewald and Ruf30  
    BMP2 Bone morphogenetic protein 2 Differentiation NM_001200 BMP-2 Riewald et al,19  Riewald and Ruf30  
    CCL2 Chemokine (C-C motif) ligand 2 Inflammation NM_002982 MCP-1 Riewald et al,19  Franscini et al33  
    CX3CL1† Chemokine (C-X3-C motif) ligand 1 Adhesion NM_002996 Fractalkine Joyce et al,15  Franscini et al,33  Brueckmann et al34  
    CXCL2 Chemokine (C-X-C motif) ligand 2 Inflammation NM_002089 MIP-2, GRO Riewald et al,19  Riewald and Ruf,30  Franscini et al33  
    DDX21 DEAD (Asp-Glu-Ala-Asp) box polypeptide 21 Transcription NM_004728 RNA helicase II/Gu-α Joyce et al15  
    F3 Coagulation factor III (thromboplastin, tissue factor) Coagulation NM_001993 TF, CD142 Riewald et al,19  Riewald and Ruf30  
    HBEGF Heparin-binding EGF-like growth factor Proliferation NM_001945 HBEGF Riewald et al19  
    IL1RI† Interleukin 1 receptor, type 1 Inflammation NM_000877 IL-1R1, CD121a Riewald and Ruf,30  Franscini et al33  
    IL6 Interleukin 6 (interferon, beta 2) Inflammation NM_000600 IL-6 Franscini et al,33  Hooper et al35  
    IL8 Interleukin 8 Inflammation NM_000584 IL-8, CXCL-8 Franscini et al,33  Hooper et al,35  Brueckmann et al36  
    NFKB1† Nuclear factor of kappa light polypeptide gene enhancer 1 Transcription NM_003998 NF-κB Joyce et al,15  Joyce and Grinnell,32  Franscini et al33  
    NFKB2† Nuclear factor of kappa light polypeptide gene enhancer 2 Transcription NM_002502 NF-κB2 p100 Joyce et al,15  Riewald and Ruf,30  Franscini et al33  
    NOS3 Nitric oxide synthase 3 (endothelial cell) Inflammation NM_000603 eNOS Joyce et al15  
    NR4A1 Nuclear receptor subfamily 4, group A, member 1 Apoptosis NM_173157 TR3, Nur77, NA4A1 Riewald et al,19  Riewald and Ruf,30  Franscini et al33  
    NR4A2 Nuclear receptor subfamily 4, group A, member 2 Transcription NM_006186 NURR1, NA4A2 Riewald et al,19  Riewald and Ruf30  
    NR4A3 Nuclear receptor subfamily 4, group A, member 3 Transcription NM_006981 NOR-1, NA4A3 Riewald et al,19  Riewald and Ruf30  
    PCNA Proliferating cell nuclear antigen Cell cycle NM_002592 PCNA Joyce et al15  
    PTGS2 Prostaglandin-endoperoxide synthase 2 Inflammation NM_000963 COX-2 Riewald et al,19  Riewald and Ruf,30  Brueckmann et al37  
    SMAD3 SMAD, mothers against DPP homolog 3 (Drosophila) Apoptosis NM_005902 SMAD-3 Joyce et al15  
    TNFAIP3 Tumor necrosis factor, alpha-induced protein 3 Apoptosis NM_006290 A20 Joyce et al,15  Riewald et al19  
Down-regulation      
    B2M Beta-2-microglobulin Inflammation NM_004048 B2M Joyce and Grinnell32  
    BIRC5 Baculoviral IAP repeat-containing 5 (survivin) Apoptosis NM_001168 Survivin Joyce and Grinnell,32  Franscini et al33  
    CALR Calreticulin Inflammation NM_004343 Ro, cC1qR Joyce et al,15  Joyce and Grinnell32  
    CMKOR1 Chemokine orphan receptor 1 Cell signaling NM_020311 RDC1 Joyce et al15  
    CX3CL1† Chemokine (C-X3-C motif) ligand 1 Adhesion NM_002996 Fractalkine Joyce et al,15  Franscini et al,33  Brueckmann et al34  
    EFNA1 Ephrin-A1 Chemoattract NM_004428 Ephrin-A1 Joyce et al15  
    ICAM1 Intercellular adhesion molecule 1 (CD54) Adhesion NM_000201 ICAM-1, CD54 Joyce et al,15  Franscini et al33  
    IL1R1† Interleukin 1 receptor, type I Inflammation NM_000877 IL-1R1, CD121a Riewald and Ruf,30  Franscini et al33  
    LTB Lymphotoxin beta (TNF superfamily, member 3) Inflammation NM_002341 LT-β Joyce and Grinnell32  
    MMP10 Matrix metallopeptidase 10 (stromelysin 2) Proteolysis NM_002425 MMP-10 Joyce et al15  
    NFKB1† Nuclear factor of kappa light polypeptide gene enhancer 1 Transcription NM_003998 NF-κB Joyce et al,15  Joyce and Grinnell,32  Franscini et al33  
    NFKB2† Nuclear factor of kappa light polypeptide gene enhancer 2 Transcription NM_002502 NF-κB2 p100 Joyce et al,15  Riewald and Ruf30  
    SELE Selectin E (endothelial adhesion molecule 1) Adhesion NM_000450 E-selectin, CD62E Joyce et al,15  Franscini et al33  
    SOD2 Superoxide dismutase 2, mitochondrial Oxidation NM_000636 MnSOD Joyce et al15  
    THBS1‡ Thrombospondin 1 Adhesion NM_003246 TSP-1 Riewald and Ruf30  
    TP53‡ Tumor protein p53 (Li-Fraumeni syndrome) Apoptosis NM_000546 p53 Cheng et al,16  Riewald and Ruf,30  Guo et al31  
    VCAM1 Vascular cell adhesion molecule 1 Adhesion NM_080682 VCAM-1, CD106 Joyce et al,15  Franscini et al33  

eNOS indicates endothelial nitric oxide synthase.

*

Selected genes whose expression is modulated by APC. Genes were selected from available microarray data. Gene selection criteria are based on at least 2-fold up-regulation or down-regulation by APC and independent confirmation of the gene array results. The list is not a complete list of all potentially important changes in gene expression. Nomenclature according to HUGO gene nomenclature committee.

†

These genes are down-regulated by APC in TNFα-stimulated human umbilical vein endothelial cells (HUVECs) but up-regulated by APC when human coronary artery endothelial cells (HCAECs) are stimulated with a mixture of interleukin-1β, TNFα, and interferon-γ.15,33 

‡

Modulation of the expression of thrombospondin-1 and p53 by APC in the microarray analysis was less than 2-fold. Nevertheless, APC-induced changes in these genes are shown to be functionally significant and are herein included (see “APC-mediated alteration of gene expression profiles”).

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