Supplementary Table 1 Primers used for real-time RT-PCR
Gene / Sense / Anti-SenseP53 / CTCTCCCCCGCAAAAGAAAAA / CTCCTCTGTAGCATGGGCATC
P21 / ACGTGGCCTTGTCGCTGTCTT / ATGGAATCTGCGCTTGGAGTGA
Fas / TATCAAGGAGGCCCATTTTGC / TGTTTCCACTTCTAAACCATGCT
Bax / CCGGCGAATTGGAGATGAACT / CCAGCCCATGATGGTTCTGAT
CylinD1 / GCGTACCCTGACACCAATCTC / CTCCTCTTCGCACTTCTGCTC
Egfr / CCAAGGCACAAGTAACAGGCT / CCACGGTGTTGAGGGCAAT
Igf2 / GGGACGTGTCTACCTCTCAGG / GACGATGACGTTTGGCCTCTC
P16 / CGCAGGTTCTTGGTCACTGT / TGTTCACGAAAGCCAGAGCG
Trail-R/DR5 / TGTTCCAGTAACAGCTAACCCA / CTGGTGTAGTCAATACCCTCTCT
c-Fos / CGGGTTTCAACGCCGACTA / TTGGCACTAGAGACGGACAGA
c-myc / CCGTCCTCGGATTCTC / ATGCAGGGATGATGTTCTGG
Supplementary Table 2 Primers used for promoter analysis
Gene / Anti-Sense / Anti-Sensep53 / AACGCGTGGGTGAACTGGCATTAACGGG / AAGATCTTCTCAGGCAAGGGGAGGATACAG
Fas / TTGGCCAACGATTCAATTAGATGC / ATGTCTGCAGCAAGGGAAAACAGC
Bax / CCTGGCCTGCTGCTACTTCACATT / GCCGGAGGGGTCCTAGGGTTCTT
Trail-R/DR5 / CAGCCCCATCCAGTTTCCAGGTAT / AGCTCCCAAAAGCCACGAAGGAT
c-Fos / TCATACGCGTCCCTGGCGGCGCTGTGTTGCTGTA / ACTGAGATCTTCGCGGAACCGCCGGCTCTATCC
Supplementary Table 3 Aberrantly expressed genes in tumors compared with normal salivary glands from wide-type mice
UpregulatedGeneBank / Symbol / Description / Signaling Pathway / Value
NM_007527 / Bax / Bcl2-associated X protein / DNA Damage/P53 pathway / 9.027E+2,5.323E+1
NM_007669 / p21Waf1/p21cip / Cyclin-dependent kinase inhibitor 1A (P21) / DNA Damage/P53 pathway
Hypoxia pathway
TGF-beta pathway
Androgen pathway / 1.006E+2,7.466E+1
NM_008343 / Igfbp3 / Insulin-like growth factor binding protein 3 / DNA Damage/P53 pathway
Hypoxia pathway / 5.868E+1,4.268E+1
NM_010786 / Mdm2 / Transformed mouse 3T3 cell double minute 2 / DNA Damage/P53 pathway / 4.023E+0,3.558E+0
NM_009517 / Wig1 / Wild-type p53-induced gene 1 / DNA Damage/P53 pathway / 2.286E+0,N/A
NM_007987 / Fas / Tumor necrosis factor receptor superfamily, member 6 / DNA Damage/P53 pathway / 3.373E+2,N/A
NM_009715 / CRE-BP/Creb2 / Activating transcription factor 2 / Stress/ p38&JNK pathway / 1.303E+0,7.940E+0
NM_007742 / Cola1 / Procollagen, type I, alpha 1 / Stress/ p38&JNK pathway
MAP Kinase pathway / 1.687E+0,3.511E+0
NM_010234 / c-fos / FBJ osteosarcoma oncogene / Stress/ p38&JNK pathway
Cox-2 pathway
MAP Kinase pathway / 3.325E+1,3.376E+0
NM_010849 / c-myc / Myelocytomatosis oncogene / Stress/ p38&JNK pathway
PI-3 Kinase/AKT pathway
Wnt pathway / 8.752E+0,7.835E+0
NM_011640 / p53 / Transformation related protein 53 / Stress/ p38&JNK pathway / 5.567E+0,3.771E+2
NM_013560 / Hsp25 / Heat shock protein / Stress /HeatShock pathway
Stress/ p38&JNK pathway / 1.486E+0,3.123E+1
NM_024441 / Hspb2 / Heat shock protein 2 / Stress /HeatShock pathway Stress/ p38&JNK pathway / 2.586E+0,3.789E+0
NM_009652 / AKT-1 / Thymoma viral proto-oncogene 1 / Survival/NF-kB pathway / 1.956E+0,3.657E+0
NM_009397 / TNFAIP3 / Tumor necrosis factor, alpha-induced protein 3 / Survival/NF-kB pathway / 7.080E+1,3.702E+1
NM_007631 / Cyclin D1 / Cyclin D1 / PI-3 Kinase/AKT pathway
Wnt pathway / 2.408E+0,1.222E+1
XM_129845 / Fn1 / Mouse fibronectin (FN) mRNA / PI-3 Kinase/AKT pathway / 4.470E+0,1.092E+1
NM_010591 / c-JUN / Jun oncogene / PI-3 Kinase/AKT pathway
MAP Kinase pathway
Wnt pathway / 5.926E+0,1.106E+1
NM_009877 / p16ink4a / Cyclin-dependent kinase inhibitor 2A / TGF-beta pathway / 1.522E+1,4.904E+0
NM_007670 / p15INK4b / Cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) / TGF-beta pathway / 4.127E+0,8.642E+0
NM_007671 / p18 / Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) / TGF-beta pathway / 7.474E+1,2.886E+1
NM_011146 / Pparg / Peroxisome proliferator activated receptor gamma / Cox-2 pathway / 1.577E+3,N/A
NM_020275 / TRAIL-R/DR5 / Tumor necrosis factor receptor superfamily, member 10b / Cox-2 pathway / 8.700E+2,3.443E+1
NM_010493 / ICAM-1 / Intercellular adhesion molecule / Inflammation/
NF-kB pathway / 1.181E+1,6.538E+2
NM_008366 / IL-2 / Interleukin 2 / Inflammation/
NF-kB pathway / 2.208E+0,3.049E+0
NM_007913 / Krox-24(EGR-1) / Mouse Early growth response 1 / MAP Kinase pathway / 1.609E+1,6.958E+1
NM_009972 / Beta-casein / Casein beta / Stat pathway / 1.911E+0,1.327E+1
NM_010557 / IL-4R / Interleukin 4 receptor, alpha / Stat pathway / 8.717E+0,2.087E+2
NM_010496 / ID2 / Inhibitor of DNA binding 2 / Wnt pathway / 1.423E+0,4.151E+0
NM_007912 / EGFR / Epidermal growth factor receptor / Estrogen pathway
Androgen pathway / 1.321E+2,2.211E+1
D63902 / EFP/Zfp147 / Tripartite motif protein 25 / Estrogen pathway / 1.024E+1,3.091E+0
NM_022995 / N4wbp4T/MEPAI / Nedd4 WW binding protein 4 / Androgen pathway / 3.337E+1,1.019E+1
NM_010442 / HMOX1 / Heme oxygenase (decycling) 1 / Hypoxia pathway / 4.695E+1,1.253E+1
NM_011400 / Glucose transporter 1 / Solute carrier family 2 (facilitated glucose transporter), member 1 / Hypoxia pathway / 1.559E+1,2.667E+0
NM_133977 / Transferrin / Transferrin / Hypoxia pathway / 4.358E+0,3.558E+0
NM_011638 / Tfr1 / Transferrin receptor / Hypoxia pathway / 6.238E+0,1.423E+0
NM_008957 / Patched / Patched homolog / Hedgehog pathway / 3.629E+1,N/A
NM_019653 / WSB-1 / WD-40-repeat-containing protein with a SOCS box 1 / Hedgehog pathway / N/A,6.390E+0
Downregulated
GeneBank / Symbol / Description / Signaling Pathway / Value
NM_009741 / Bcl-2 / B-cell leukemia/lymphoma 2 / DNA Damage/P53 pathway
PI-3 Kinase/AKT pathway
Stat pathway
Estrogen pathway / -0.000E-1,1.487E-1
NM_009425 / Trail / TNF-related apoptosis inducing ligand / DNA Damage/P53 pathway
PI-3 Kinase/AKT pathway / 1.724E-1,N/A
NM_009421 / TRAF1 / Tnf receptor-associated factor 1 / DNA Damage/P53 pathway
Survival/NF-kB pathway / -0.000E-1,6.003E-1
NM_015744 / autotaxin (ATX) / Mus musculus ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2) / Stress/ p38&JNK pathway
Wnt pathway / 4.129E-3,2.758E-1
NM_008670 / NAIP1 / Baculoviral IAP repeat-containing 1a / Survival/NF-kB pathway / -0.000E-1,-0.000E-1
NM_010872 / NAIP2 / Baculoviral IAP repeat-containing 1b / Survival/NF-kB pathway / -0.000E-1,-0.000E-1
NM_010870 / NAIP5 / Baculoviral IAP repeat-containing 1e / Survival/NF-kB pathway / 6.580E-2,2.651E-1
NM_009876 / p57Kip2 / Cyclin-dependent kinase inhibitor 1C (P57) / TGF-beta pathway / 7.674E-3,2.676E-1
NM_008599 / MIG/Scyb9 / Chemokine (C-X-C motif) ligand 9 / Stat pathway / 3.287E-4,1.045E-1
NM_007376 / A1m / Pregnancy zone protein / Stat pathway / N/A,1.811E-3
NM_009327 / Tcf1 / Transcription factor 1 / Wnt pathway / N/A,1.726E-3
NM_018865 / ELM1 (Wisp-1) / WNT1 inducible signaling pathway protein 1 / Wnt pathway / -0.000E-1,N/A
NM_008829 / progesterone receptor / Mus musculus progesterone receptor / Estrogen pathway / N/A,-0.000E-1
NM_016770 / Folh1 / Folate hydrolase / Androgen pathway / 1.075E-3,1.786E-2
NM_008455 / Kallikrein 3 / Kallikrein B, plasma 1 / Androgen pathway / 5.937E-2,-0.000E-1
NM_010104 / Edn1 / Endothelin 1 / Hypoxia pathway / 1.838E-1,2.263E-1
NM_010927 / iNOS / Nitric oxide synthase 2, inducible, macrophage / Hypoxia pathway
Inflammation/NF-kB pathway
Stat pathway / 1.890E-1,-0.000E-1
NM_007553 / BMP2 / Bone morphogenetic protein 2 / Hedgehog pathway / 8.003E-2,-0.000E-1
NM_007554 / BMP4 / Bone morphogenetic protein 4 / Hedgehog pathway
Wnt pathway / -0.000E-1,8.971E-2
NM_021279 / Wnt1 / Wingless-related MMTV integration site 1 / Hedgehog pathway
Wnt pathway / -0.000E-1,4.190E-2
NM_023653 / Wnt2 / Wingless-related MMTV integration site 2 / Hedgehog pathway / N/A,1.909E-1
NM_010446 / HNF3B/forkhead / Forkhead box A2 / Hedgehog pathway / -0.000E-1,1.575E-2
NM_020259 / hip / Hedgehog-interacting protein / Hedgehog pathway / 2.467E-1
Supplementary Table 4 Aberrantly expressed genes in tumors comparing with normal salivary glands from PLAG1 transgenic mice
UpregulatedGeneBank / Symbol / Description / Signaling Pathway / Value
NM_011075 / ABCB1 / ATP-binding cassette, sub-family B (MDR/TAP), member 1B / Stress / p38 & JNK Pathways
Wnt Pathway / 1.735E+1, N/A
NM_009652 / AKT-1 / Thymoma viral proto-oncogene 1 / Survival/NF-kB pathway / 3.607E+0, 2.123E+0
NM_007631 / Cyclin D1 / Cyclin D1 / PI-3 Kinase/AKT pathway
Wnt pathway / 3.879E+0, 1.385E+0
NM_009517 / Wig1 / Wild-type p53-induced gene 1 / DNA Damage/P53 pathway / 1.905E+1, 2.915E+0
NM_007987 / Fas / Tumor necrosis factor receptor superfamily, member 6 / DNA Damage/P53 pathway / 9.217E+1, 1.670E+0
NM_020275 / TRAIL-R/DR5 / Tumor necrosis factor receptor superfamily, member 10b / Cox-2 pathway / 1.752E+2, N/A
NM_011400 / Glucose transporter 1 / Solute carrier family 2 (facilitated glucose transporter), member 1 / Hypoxia pathway / 5.208E+0, 1.006E+1
NM_011198 / Cox-2 / Prostaglandin-endoperoxide synthase 2 / Cox-2 pathway / 9.847E+2, N/A
NM_011146 / Pparg / Peroxisome proliferator activated receptor gamma / Cox-2 pathway / 5.624E+0, 1.526E+0
NM_022995 / N4wbp4T/MEPAI / Nedd4 WW binding protein 4 / Androgen pathway / 1.137E+1, 2.227E+0
NM_010557 / IL-4R / Interleukin 4 receptor, alpha / Stat pathway / 1.978E+2, 5.709E+2
NM_008343 / Igfbp3 / Insulin-like growth factor binding protein 3 / DNA Damage/P53 pathway
Hypoxia pathway / 2.901E+1, 1.491E+1
NM_010493 / ICAM-1 / Intercellular adhesion molecule / Inflammation/
NF-kB pathway / 1.860E+1, 6.099E+0
NM_024441 / Hspb2 / Heat shock protein 2 / Stress /HeatShock pathway Stress/ p38&JNK pathway / 5.823E+0, 1.755E+0
NM_013560 / Hsp25 / Heat shock protein 1 / Stress /HeatShock pathway Stress/ p38&JNK pathway / 3.776E+2, N/A
NM_008296 / Hsf1 (tcf5) / Heat shock factor 1 / Stress / Heat Shock Pathway / 3.501E+0, 3.256E+0
NM_010442 / HMOX1 / Heme oxygenase (decycling) 1 / Hypoxia pathway / 4.308E+1, 5.187E+0
NM_010235 / Fra1 / Fos-like antigen 1 / Wnt Pathway / 2.709E+0, N/A
NM_010234 / c-fos / FBJ osteosarcoma oncogene / Stress/ p38&JNK pathway
Cox-2 pathway
MAP Kinase pathway / 1.545E+1, N/A
NM_007913 / Krox-24 / Mouse Early growth response 1 / MAP Kinase pathway / 1.094E+1, 2.539E+0
NM_007912 / EGFR / Epidermal growth factor receptor / Estrogen pathway
Androgen pathway / 6.071E+1, 2.014E+2
NM_007670 / p15INK4b / Cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) / TGF-beta pathway / 4.241E+0, 2.018E+0
NM_009877 / p16ink4a / Cyclin-dependent kinase inhibitor 2A / TGF-beta pathway / 5.556E+0, 4.496E+0
NM_007669 / p21Waf1/p21cip / Cyclin-dependent kinase inhibitor 1A (P21) / DNA Damage/P53 pathway
Hypoxia pathway
TGF-beta pathway
Androgen pathway / 5.715E+0, N/A
NM_019653 / WSB-1 / WD-40-repeat-containing protein with a SOCS box 1 / Hedgehog pathway / 3.350E+0, 4.828E+0
Downregulated
GeneBank / Symbol / Description / Signaling Pathway / Value
NM_009741 / Bcl-2 / B-cell leukemia/lymphoma 2 / DNA Damage/P53 pathway
PI-3 Kinase/AKT pathway
Stat pathway
Estrogen pathway / 8.426E-3
NM_009425 / Trail / TNF-related apoptosis inducing ligand / DNA Damage/P53 pathway
PI-3 Kinase/AKT pathway / 7.458E-1, 9.883E-2
NM_008958 / Patched 2 / Patched (Drosophila) homolog 2 / Hedgehog Pathway / 2.090E-2
NM_008957 / Patched / Patched homolog / Hedgehog pathway / 4.059E-1, 2.995E-2
NM_008829 / Progesterone receptor / Mus musculus progesterone receptor / Estrogen pathway / -0.000E-1, N/A
NM_010927 / iNOS / Nitric oxide synthase 2, inducible, macrophage / Hypoxia pathway
Inflammation/NF-kB pathway
Stat pathway / 1.419E-2, -0.000E-1
NM_010810 / MMP7 / Matrix metalloproteinase 7 / PI-3 Kinase / AKT Pathway
Wnt Pathway / 5.893E-4
NM_019471 / Stromelysin 2 / Matrix metalloproteinase 10 / STAT Pathway / -0.000E-1, 5.445E-2
NM_008455 / Kallikrein 3 / Kallikrein B, plasma 1 / Androgen Pathway / 4.013E+0, -0.000E-1
NM_008390 / IRF-1 / Interferon regulatory factor 1 / STAT Pathway / 1.231E+0, 2.769E-1
NM_020259 / Hip / Hedgehog-interacting protein / Hedgehog pathway / 2.516E-1, 1.838E-1
NM_016770 / Folh1 / Folate hydrolase / Androgen pathway / 1.385E-3, 9.806E-3
NM_015744 / autotaxin (ATX) / Mus musculus ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2) / Stress/ p38&JNK pathway
Wnt pathway / 4.684E-3, 8.935E-2
NM_010104 / Edn1 / Endothelin 1 / Hypoxia pathway / 8.081E-2, N/A
NM_008599 / MIG/Scyb9 / Chemokine (C-X-C motif) ligand 9 / Stat pathway / 4.565E-4, 4.271E-2
NM_009876 / p57Kip2 / Cyclin-dependent kinase inhibitor 1C (P57) / TGF-beta pathway / 8.790E-4, 3.827E-3
NM_009764 / BRCA1 / Breast cancer 1 / Estrogen Pathway / N/A, -0.000E-1
NM_007554 / BMP 4 / Bone morphogenetic protein 4 / Hedgehog pathway
Wnt pathway / -0.000E-1, 1.970E-2
NM_007553 / BMP2 / Bone morphogenetic protein 2 / Hedgehog pathway / 1.077E-2, -0.000E-1
NM_008670 / NAIP1 / Baculoviral IAP repeat-containing 1a / Survival/NF-kB pathway / -0.000E-1, -0.000E-1
NM_010872 / NAIP2 / Baculoviral IAP repeat-containing 1b / Survival/NF-kB pathway / -0.000E-1, -0.000E-1
NM_010870 / NAIP5 / Baculoviral IAP repeat-containing 1e / Survival/NF-kB pathway / 2.372E-2, 8.721E-2
NM_007536 / Bfl-1 / B-cell leukemia/lymphoma 2 related protein A1d / Survival / NFkB Pathway / 7.381E-2, 8.075E-1
Supplementary Table 5 Aberrantly expressed genes in normal salivary glands from PLAG1 transgenic mice compared with normal salivary glands from wide-type mice
UpregulatedGeneBank / Symbol / Description / Signaling Pathway / Value
NM_007527 / Bax / Bcl2-associated X protein / DNADamage/P53 pathway / 1.850E+3, 2.900E+1
NM_019653 / WSB-1 / WD-40-repeat-containing protein with a SOCS box 1 / Hedgehog pathway / N/A, 1.323E+0
NM_011638 / Tfr1 / Transferrin receptor / Hypoxia pathway / 6.413E+0, 1.410E+0
NM_133977 / Transferrin / Transferrin / Hypoxia pathway / 3.286E+0, 3.598E+0
NM_007987 / Fas / Tumor necrosis factor receptor superfamily, member 6 / DNA Damage/P53 pathway / 3.660E+0, N/A
NM_008957 / Patched / Patched homolog / Hedgehog pathway / 8.940E+1, N/A
NM_011146 / Pparg / Peroxisome proliferator activated receptor gamma / Cox-2 pathway / 2.804E+2, N/A
NM_010786 / Mdm2 / Transformed mouse 3T3 cell double minute 2 / DNA Damage/P53 pathway / 2.607E+0, 2.468E+0
NM_007913 / Krox-24(Egr-1) / Mouse Early growth response 1 / MAP Kinase pathway / 1.471E+0, 2.741E+1
NM_009972 / Beta-casein / Casein beta / Stat pathway / 9.074E+0, 2.955E+0
NM_007671 / p18 / Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) / TGF-beta pathway / 6.358E+1, 4.524E+0
NM_009876 / p57Kip2 / Cyclin-dependent kinase inhibitor 1C (P57) / TGF-beta pathway / 8.730E+0, 6.991E+1
NM_007554 / BMP 4 / Bone morphogenetic protein 4 / Hedgehog pathway
Wnt pathway / 3.899E+3, 4.554E+0
NM_007553 / BMP2 / Bone morphogenetic protein 2 / Hedgehog pathway / 7.433E+0, 6.042E+0
NM_007464 / IAP1 / Baculoviral IAP repeat-containing 2 / Survival / NFkB Pathway / 6.671E+0, 1.254E+1
NM_010870 / NAIP5 / Baculoviral IAP repeat-containing 1e / Survival/NF-kB pathway / 2.774E+0, 3.040E+0
NM_009743 / Bcl-x / Bcl2-like / Survival / NFkB Pathway / 1.728E+0, 7.668E+0
NM_007536 / Bfl-1 / B-cell leukemia/lymphoma 2 related protein A1d / Survival / NFkB Pathway / 5.736E+0, 3.652E+1
NM_009741 / Bcl-2 / B-cell leukemia/lymphoma 2 / DNA Damage/P53 pathway
PI-3 Kinase/AKT pathway
Stat pathway
Estrogen pathway / 2.915E+1, 1.764E+1
Downregulated
GeneBank / Symbol / Description / Signaling Pathway / Value
NM_011076 / ABCB4 / ATP-binding cassette, sub-family B (MDR/TAP), member 1A / Wnt Pathway / 2.177E-4, 2.405E-1
NM_023653 / Wnt2 / Wingless-related MMTV integration site 2 / Hedgehog Pathway / N/A, -0.000E-1
NM_021279 / Wnt1 / Wingless-related MMTV integration site 1 / Hedgehog pathway
Wnt pathway / -0.000E-1, 6.412E-3
NM_018865 / ELM1 (Wisp-1) / WNT1 inducible signaling pathway protein 1 / Wnt pathway / 2.035E-2, N/A
NM_009421 / TRAF1 / Tnf receptor-associated factor 1 / DNA Damage/P53 pathway
Survival/NF-kB pathway / 1.088E-3, 1.440E+0
NM_009327 / Tcf1 / Transcription factor 1 / Wnt pathway / N/A, -0.000E-1
NM_007376 / A1m / Pregnancy zone protein / Stat pathway / N/A, 3.826E-2
NM_010557 / IL-4R / Interleukin 4 receptor, alpha / Stat pathway / 4.408E-2, 3.656E-1
NM_021283 / IL-4 / Interleukin 4 / STAT Pathway / 7.842E-1, 2.876E-2
NM_013560 / Hsp25 / Heat shock protein 1 / Stress /HeatShock pathway
Stress/ p38&JNK pathway / 3.936E-3, -0.000E-1
NM_008296 / Hsf1 (tcf5) / Heat shock factor 1 / Stress / Heat Shock Pathway / 2.034E-1, 1.525E-1
NM_010446 / HNF3B/forkhead / Forkhead box A2 / Hedgehog pathway / -0.000E-1, 5.784E-3
NM_010235 / Fra1 / Fos-like antigen 1 / Wnt Pathway / 1.265E-1, -0.000E-1
NM_010234 / c-Fos / FBJ osteosarcoma oncogene / Stress/ p38&JNK pathway
Cox-2 pathway
MAP Kinase pathway / -0.000E-1
NM_007912 / EGFR / Epidermal growth factor receptor / Estrogen pathway
Androgen pathway / 1.098E-1
NM_008670 / NAIP1 / Baculoviral IAP repeat-containing 1a / Survival/NF-kB pathway / 3.513E-2, 5.576E-1
NM_011075 / ABCB1 / ATP-binding cassette, sub-family B (MDR/TAP), member 1B / Wnt Pathway / -0.000E-1, 2.767E-2
Supplementary Fig.1 Results of cluster analysis