Your SlideShare is downloading. ×
Emt and ecm 2013
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Emt and ecm 2013

320
views

Published on


0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
320
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
11
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Sample & Assay Technologies EMT and ECM Jesse Liang, Ph.D.
  • 2. Sample & Assay Technologies Epithelial Cells 1. Closely adjoined 2. Polarized Epithelial Markers: E-Cadherin (adherens junctions) Claudins (tight junctions) Occludin (tight junctions) Desmoplakin (desmosomes) Cytokeratin-8, -18 and -19 Mucin-1 There are 5 different types of cell junctions. They are tight junctions, adherens junctions, desmosomes, hemidesmosomes, and gap junctions.
  • 3. Sample & Assay Technologies Mesenchymal Cells 1. Not adjoined 2. No polarity Mesenchymal Markers: Vimentin N-Cadherin Fibronectin Vitronectin FSP1(fibroblast-specific protein 1) Smooth-muscle actin FGFR2 IIIb and IIIc splice variants
  • 4. Sample & Assay Technologies EMT (Epithelial-Mesenchymal Transition) Epithelial cells can convert into mesenchymal cells by a process known as EMT, which disrupts cell-cell adhesion and cell-ECM adhesion. Cell remodeling + ECM remodeling * Embryogenesis and development * Cancer * Fibrosis
  • 5. Sample & Assay Technologies The Nature of EMT 1. transient and reversible 2. highly context-specific 3. a vicious cycle in pathological conditions
  • 6. Sample & Assay Technologies Epithelial-Mesenchymal Transitions in Development and Disease Cell (2009) 139, 871-890. Activators and Suppressors of EMT highly context-specific TGFβ, FGF, EGF families, HGF; Src, GTPase family – Ras, Rho, Rac; Snail, Slug, Twist, ZEB, NFκB Extracellular Cytoplasmic Nuclear
  • 7. Sample & Assay Technologies TGF-β and EMT & ECM TGF-β is the best characterized and most often used inducer of EMT. Other heavily involved signaling pathways of EMT include PI3K-Akt, GPCR, MAPK, Wnt, Notch, Hedgehog, NFκB, HIF, integrins, and growth factors. TGF-β is also one of the key cytokines in regulating ECM, not only by regulating expression of ECM structural proteins, but also by affecting enzymes involved in ECM biosynthesis and degradation.
  • 8. Sample & Assay Technologies Wilm’s tumor gene 1, In heart development EMT Signaling Oxygen-dependent gene expression in development and cancer: lessons learned from the Wilm’s tumor gene, WT1. Front Mol Neurosci (2011), 4:1-11.
  • 9. Sample & Assay Technologies EMT and Cancer • Progression of most carcinomas is associated with the acquisition of mesenchymal phenotype. • Cells with an EMT phenotype induced by different factors are rich sources for cancer stem-like cells. • Moreover, induction of EMT in tumor cells not only promotes invasion and metastasis but also contributes to drug resistance.
  • 10. Sample & Assay Technologies Induction of EMT Generates Stem-Like Cells Breast cancer – initiating cells are CD44+CD24- cells. EMT phenotype EMT induction Mani SA, et al. The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells. Cell (2008), 133, 704-715. Leukemia – initiating cells are CD34+CD38- cells. Colon cancer – initiating cells are CD133+ cells. Brain cancer – initiating cells are CD133+ cells. Prostate cancer – initiating cells are CD44+α2β1+ cells.
  • 11. Sample & Assay Technologies miRNAs Link EMT to Stem-Like Cells in Human Cancers miR-200 family and ZEB1/2 miR-200a * Knockdown of Akt-1 decreases the expression of miR-200 family including miR200a, and increases mammosphere forming ability in breast cancer miR-200b * miR-200b inhibits expression of ZEB1, ZEB2, Lin28B and Notch1 in prostate cancer * miR-200b targets Suz12 and contributes to cancer stem cells maintenance in breast cancer miR-200c * miR-200c inhibits expression of ZEB1, ZEB2 and Bmi1 in breast cancer; * miR-200c inhibits expression of ZEB1, Sox2, Bmi1 and KLF4 in pancreatic cancer miR-183 * ZEB1 represses miR-183 expression, which increases the expression of Bmi1 and KLF4 in pancreatic cancer miR-203 * ZEB1 represses miR-203 expression, which increases the expression of Bmi1 and KLF4 in pancreatic cancer
  • 12. Sample & Assay Technologies miR-200 Links EMT to ECM • Several miRNAs have been identified as either oncogenes (miR-17– 92, miR-155, miR-21) or tumor suppressors (miR-15a, miR-16a, let-7) and some human tumor types can be classified by miRNA signatures. • The miR-200 family of miRNAs consists of five members (miR-200a, 200b, miR-200c, 141, 429) that have been demonstrated to have a role in EMT through regulation with the ZEB transcription factors and regulation of E-cadherin and vimentin expression. • The most striking effect of miR-200 expression was a change in protein constituents in the media resulting from protein secretion and shedding with downregulation of extracellular matrix, peptidases and cell adhesion proteins. • Proteins upregulated with miR-200 restoration were associated primarily with cytoskeletal regulation and cell adhesion. - Cancer Research (2011) Dec 15; 71(24): 7670–7682
  • 13. Sample & Assay Technologies EMT and Fibrosis Fibrosis is characterized by the presence of an excess of fibrous connective tissue in an organ, and in particular by an excessive deposition of collagen I. Renal fibrosis, for example, has been associated with the activation of interstitial fibroblasts, which give rise to collagen secreting myofibroblasts. In addition, myofibroblasts can also originate from renal tubular epithelial and endothelial cells that undergo EMT. Activation of Snail1, a well known EMT inducer, leads to renal fibrosis and renal failure in animal models. High Snail1 expression and evidence of EMT has also been found in the kidneys of patients with renal fibrosis (Boutet et al, 2006).
  • 14. Sample & Assay Technologies Cancer and Fibrosis are (Induced by) Inflammation In the context of a chronic inflammatory condition, TGFβ1 and hypoxia activate EMT that converges in the activation of NFκB, which is also induced by the inflammatory cytokines and oxidative stress.
  • 15. Sample & Assay Technologies Inflammation, Oxidative Stress and Hypoxia in EMT Induction Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Molecular Medicine (2009), 1, 303-314.
  • 16. Sample & Assay Technologies PCR Array Introduction 84 Pathway-Specific Genes of Interest 5 Housekeeping Genes Genomic DNA Contamination Control Reverse Transcription Controls (RTC) n=3 Positive PCR Controls (PPC) n=3
  • 17. Sample & Assay Technologies EMT PCR Arrays http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-090Z.html Genes Up-Regulated During EMT: AHNAK, BMP1, CALD1, CAMK2N1, CDH2, COL1A2, COL3A1, COL5A2, FN1, FOXC2, GNG11, GSC, IGFBP4, ITGA5, ITGAV, MMP2, MMP3, MMP9, MSN, SERPINE1, SNAI1, SNAI2, SNAI3, SOX10, SPARC, STEAP1, TCF4, TIMP1, TMEFF1, TMEM132A, TWIST1, VCAN, VIM, VPS13A, WNT5A, WNT5B. Genes Down-Regulated During EMT: CAV2, CDH1 (E-cadherin), DSP, FGFBP1, IL1RN, KRT19, MST1R, NUDT13, OCLN, PPPDE2, RGS2, SPP1 (Osteopontin), TFPI2, TSPAN13. Differentiation & Development: AKT1, BMP1, BMP2, BMP7, COL3A1, COL5A2, CTNNB1, DSP, ERBB3, F11R, FOXC2, FZD7, GSC, JAG1, KRT14, MST1R, NODAL, NOTCH1, PTP4A1, SMAD2, SNAI1, SNAI2, SOX10, TGFB2, TGFB3, TMEFF1, TWIST1, VCAN, WNT11, WNT5A, WNT5B. Morphogenesis: CTNNB1, FOXC2, JAG1, RAC1, SMAD2, SNAI1, SOX10, TGFB1, TGFB2, TGFB3, TWIST1, WNT11, WNT5A. Cell Growth & Proliferation: AKT1, BMP1, BMP7, CAV2, CTNNB1, EGFR, ERBB3, FGFBP1, FOXC2, IGFBP4, ILK, JAG1, MST1R, NODAL, PDGFRB, TGFB1, TGFB2, TGFB3, TIMP1, VCAN, ZEB1. Migration & Motility: CALD1, CAV2, EGFR, FN1, ITGB1, JAG1, MSN, MST1R, NODAL, PDGFRB, RAC1, STAT3, TGFB1, VIM. Cytoskeleton: CAV2, KRT7, MAP1B, PLEK2, RAC1, VIM. Extracellular Matrix & Cell Adhesion: BMP1, BMP7, CDH1 (E-cadherin), CDH2 (N-cadherin), COL1A2, COL3A1, COL5A2, CTNNB1, DSC2, EGFR, ERBB3, F11R, FN1, FOXC2, ILK, ITGA5, ITGAV, ITGB1, MMP2, MMP3, MMP9, PTK2, RAC1, SERPINE1 (PAI-1), SPP1 (Osteopontin), TGFB1, TGFB2, TIMP1, VCAN. Signaling Pathways: Estrogen Receptor: CAV2, ESR1 (ERa), KRT19, TGFB3. G-Protein Coupled Receptor: AKT1, FZD7, GNG11, RAC1, RGS2. Integrin-Mediated: COL3A1, ILK, ITGA5, ITGAV, ITGB1, PTK2. Notch: FOXC2, JAG1, NOTCH1. Receptor Tyrosine Kinase: EGFR, ERBB3, PDGFRB, RGS2, SPARC. TGFß / BMP: BMP1, BMP2, BMP7, COL3A1, SMAD2, TGFB1, TGFB2, TGFB3. WNT: CTNNB1, FZD7, GSK3B, WNT11, WNT5A, WNT5B. Transcription Factors: CTNNB1, ESR1 (ERa), FOXC2, GSC, NOTCH1, SIP1, SMAD2, SNAI2, SNAI3, SOX10, STAT3, TCF3, TCF4, TWIST1, ZEB1, ZEB2.
  • 18. Sample & Assay Technologies EMT Methylation PCR Arrays http://www.sabiosciences.com/dna_methylation_product/HTML/EAHS-901Z.html Genes Down-Regulated During EMT: CDH1, DSP, KRT19, MST1R, OCLN, PPPDE2, RGS2, TSPAN13. Differentiation & Development: MST1R, PTP4A1, SMAD4. Cell Growth & Proliferation: GAB1, MST1R, SEH1L, SMAD4. Extracellular Matrix & Cell Adhesion: CDH1, CTNNAL1, DSC2, EPCAM, NID2. Signal Transduction: GAB1, KRT19, MAP3K5, RGS2, SMAD4, TGIF1. Cytoskeleton: CTNNAL1, KRT7, PLEK2. Other Genes: PLSCR1, YES1.
  • 19. Sample & Assay Technologies EMT ChIP PCR Arrays – Profile Histone Codes http://www.sabiosciences.com/chipqpcr_product/HTML/GH-090A.html Genes Up-Regulated During EMT: AHNAK, BMP1, CALD1, CDH2 (N-cadherin), COL1A2, COL3A1, COL5A2, FN1, FOXC2, GNG11, GSC, IGFBP4, ITGA5, ITGAV, MMP2 (Gelatinase A), MMP3, MMP9 (Gelatinase B), MSN, SERPINE1 (PAI-1), SNAI1, SNAI2, SNAI3, SOX10, SPARC, STEAP1, TCF4, TIMP1, TMEFF1, TMEM132A, TWIST1, VCAN, VIM, VPS13A, WNT5A, WNT5B. Genes Down-Regulated During EMT: CAV2, CDH1 (E-cadherin), DSP, FGFBP1, IL1RN, KRT19, MITF, MST1R, NUDT13, PPPDE2, RGS2, SPP1 (Osteopontin), TFPI2, TSPAN13. Genes with Known Histone Modifications during EMT: Increased H3K4me3: AHNAK, AKT1, BMP1, CALD1, CAV2, CDH2 (N-cadherin), CTNNB1, FN1, FZD7, GNG11, GSK3B, IGFBP4, ILK, ITGA5, MAP1B, MITF, MMP2 (Gelatinase A), RGS2, SERPINE1 (PAI-1), SNAI1, SNAI2, SPARC, TCF4, TGFB1, TGFB2, TGFB3, TIMP1, TMEFF1, TSPAN13, VIM, VPS13A, WNT5A. Decreased H3K27me3: DSP, FGFBP1, GSC, IL1RN. Differentiation & Development: AKT1, BMP1, BMP2, BMP7, COL3A1, COL5A2, CTNNB1, DSP, ERBB3, F11R, FOXC2, FZD7, GSC, KRT14, MITF, MST1R, NODAL, NOTCH1, PTP4A1, SMAD2, SNAI1, SNAI2, SOX10, TGFB2, TGFB3, TMEFF1, TWIST1, VCAN, WNT11, WNT5A, WNT5B. Morphogenesis: CTNNB1, FOXC2, PPP3R1, RAC1, SMAD2, SNAI1, SOX10, TGFB1, TGFB2, TGFB3, TWIST1, WNT11, WNT5A. Cell Growth & Proliferation: AKT1, BMP1, BMP2, BMP7, CAV2, CTNNB1, EGFR, ERBB3, FGFBP1, FOXC2, HIF1A, IGFBP4, ILK, MST1R, NODAL, PDGFRB, TGFB1, TGFB2, TGFB3, TIMP1, VCAN. Migration & Motility: CALD1, CAV2, EGFR, FN1, ITGB1, MSN, MST1R, NODAL, PDGFRB, RAC1, STAT3, TGFB1, VIM. Cytoskeleton: CAV2, KRT7, MAP1B, PLEK2, RAC1, VIM. Extracellular Matrix & Cell Adhesion: BMP1, BMP2, BMP7, CDH1 (E-cadherin), CDH2 (N-cadherin), COL1A2, COL3A1, COL5A2, CTGF, CTNNB1, DSC2, EGFR, ERBB3, F11R, FN1, FOXC2, ILK, ITGA5, ITGAV, ITGB1, MMP2 (Gelatinase A), MMP3, MMP9 (Gelatinase B), PTK2, RAC1, SERPINE1 (PAI-1), SPP1 (Osteopontin), TGFB1, TGFB2, TIMP1, VCAN. Signaling Pathways: Estrogen Receptor: CAV2, ESR1 (ERa), KRT19, TGFB3. G-Protein Coupled Receptor: AKT1, FZD7, GNG11, RAC1, RGS2. Integrin-Mediated: COL3A1, CTGF, ILK, ITGA5, ITGAV, ITGB1, PTK2. Notch: FOXC2, NOTCH1. Receptor Tyrosine Kinase: EGFR, ERBB3, PDGFRB, RGS2, SPARC. TGFb / BMP: BMP1, BMP2, BMP7, COL3A1, SMAD2, SMAD4, TGFB1, TGFB2, TGFB3. WNT: CTNNB1, FZD7, GSK3B, WNT11, WNT5A, WNT5B. . Transcription Factors: CTNNB1, ESR1 (ERa), FOXC2, GSC, MITF, NOTCH1, SIP1, SMAD2, SNAI2, SNAI3, SOX10, STAT3, TCF4, TWIST1, ZEB2
  • 20. Sample & Assay Technologies miScript miRNA PCR Arrays http://www.sabiosciences.com/mirna_pcr_array.php miRNome (miRBase V19) Human Mouse Rat Dog Rhesus Macaque miRNome (miRBase V19) 384 Well Human Mouse Rat Dog Rhesus Macaque miFinder 96 Well Human Mouse Rat Dog Rhesus Macaque miFinder 384 Well Human Mouse Apoptosis Human Mouse Rat Brain Cancer Human Mouse Rat Breast Cancer Human Mouse Rat Cancer PathwayFinder Human Mouse Rat Cardiovascular Disease Human Mouse Rat Diabetes Human Mouse Rat Cell Differentiation & Development Human Mouse Rat Immunopathology Human Mouse Rat Inflammatory Response and Autoimmunity Human Mouse Rat Neurological Development & Disease Human Mouse Rat Ovarian Cancer Human Mouse Rat Prostate Cancer Human Mouse Rat Serum & Plasma Human Mouse Rat Serum & Plasma 384 Well Human T-Cell & B-Cell Activation Human Mouse Rat miRNA QC Human Mouse Rat Dog Rhesus Macaque
  • 21. Sample & Assay Technologies miRNA Targets PCR Arrays After miRNA expression analysis with miScript miRNA PCR Arrays, perform the following functional miRNA study. Once you have treated your cells with a microRNA mimic, inhibitor, or target protector, analyze target gene expression with the RT² Profiler miRNA Targets PCR Arrays. http://www.sabiosciences.com/miRNATargetsPCRArrays.php A miRNA target gene should meet the following criteria: Target gene expression inversely correlates with miRNA expression Transfection with a miScript miRNA mimic downregulates target gene expression Transfection with a miScript miRNA inhibitor re-activates target gene expression Transfection with a miScript target protector re-activates target gene expression
  • 22. Sample & Assay Technologies ECM (Extracellular Matrix) and Cell Adhesion PCR Arrays http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-013Z.html Cell Adhesion Molecules: Transmembrane Molecules: CD44, CDH1, HAS1, ICAM1, ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGAL, ITGAM, ITGAV, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, MMP14, MMP15, MMP16, NCAM1, PECAM1, SELE, SELL, SELP, SGCE, SPG7, VCAM1. Cell-Cell Adhesion: CD44, CDH1, COL11A1, COL14A1, COL6A2, CTNND1, ICAM1, ITGA8, VCAM1. Cell-Matrix Adhesion: ADAMTS13, CD44, ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGAL, ITGAM, ITGAV, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, SGCE, SPP1, THBS3. Other Adhesion Molecules: CNTN1, COL12A1, COL15A1, COL16A1, COL5A1, COL6A1, COL7A1, COL8A1, VCAN, CTGF, CTNNA1, CTNNB1, CTNND2, FN1, KAL1, LAMA1, LAMA2, LAMA3, LAMB1, LAMB3, LAMC1, THBS1, THBS2, CLEC3B, TNC, VTN. Extracellular Matrix Proteins: Basement Membrane Constituents: COL4A2, COL7A1, LAMA1, LAMA2, LAMA3, LAMB1, LAMB3, LAMC1, SPARC. Collagens & ECM Structural Constituents: COL11A1, COL12A1, COL14A1, COL15A1, COL16A1, COL1A1, COL4A2, COL5A1, COL6A1, COL6A2, COL7A1, COL8A1, FN1, KAL1. ECM Proteases: ADAMTS1, ADAMTS13, ADAMTS8, MMP1, MMP10, MMP11, MMP12, MMP13, MMP14, MMP15, MMP16, MMP2, MMP3, MMP7, MMP8, MMP9, SPG7, TIMP1. ECM Protease Inhibitors: COL7A1, KAL1, THBS1, TIMP1, TIMP2, TIMP3. Other ECM Molecules: VCAN, CTGF, ECM1, HAS1, SPP1, TGFBI, THBS2, THBS3, CLEC3B, TNC, VTN. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Tsau C, Ito M, Gromova A, Hoffman MP, Meech R, Makarenkova HP. Barx2 and Fgf10 regulate ocular glands branching morphogenesis by controlling extracellular matrix remodeling. Development (2011) Aug;138(15):3307-17
  • 23. Sample & Assay Technologies Cell Junctions PCR Arrays There are 5 different types of cell junctions. They are tight junctions, adherens junctions, desmosomes, hemidesmosomes, and gap junctions. Focal Adhesions http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-145Z.html Tight Junctions http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-143Z.html Adherens Junctions http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-146Z.html Gap Junctions http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-144Z.html
  • 24. Sample & Assay Technologies Cancer Metastasis / Cell Motility PCR Arrays Cancer Metastasis PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-028Z.html Cell Motility PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-128Z.html ----------------------------------------------------------------------------------------------------------Zhu W, Cai MY, Tong ZT, Dong SS, Mai SJ, Liao YJ, Bian XW, Lin MC, Kung HF, Zeng YX, Guan XY, Xie D. Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymal transition. Gut (2012) Apr;61(4): 562-575.
  • 25. Sample & Assay Technologies Fibrosis PCR Arrays http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-120Z.html Pro-Fibrotic: ACTA2 (a-SMA), AGT, CCL11 (Eotaxin), CCL2 (MCP-1), CCL3 (MIP-1a), CTGF, GREM1, IL13, IL13RA2, IL4, IL5, SNAI1 (Snail). Anti-Fibrotic: BMP7, HGF, IFNG, IL10, IL13RA2. Extracellular Matrix & Cell Adhesion: ECM Components: COL1A2, COL3A1. Remodeling Enzymes: LOX, MMP1 (Collagenase 1), MMP13, MMP14, MMP2 (Gelatinase A), MMP3, MMP8, MMP9 (Gelatinase B), PLAT (tPA), PLAU (uPA), PLG, SERPINA1 (a1-antitrypsin), SERPINE1 (PAI-1), SERPINH1, TIMP1, TIMP2, TIMP3, TIMP4. Cellular Adhesion: ITGA1, ITGA2, ITGA3, ITGAV, ITGB1, ITGB3, ITGB5, ITGB6, ITGB8. Inflammatory Cytokines & Chemokines: CCL11 (Eotaxin), CCL2 (MCP-1), CCL3 (MIP-1a), CCR2, CXCR4, IFNG, IL10, IL13, IL13RA2, IL1A, IL1B, IL4, IL5, ILK, TNF. Growth Factors: AGT, CTGF, EDN1, EGF, HGF, PDGFA, PDGFB, VEGFA. Signal Transduction: TGFß Superfamily: BMP7, CAV1, DCN, ENG (EVI-1), GREM1, INHBE, LTBP1, SMAD2, SMAD3, SMAD4, SMAD6, SMAD7, TGFB1, TGFB2, TGFB3, TGFBR1 (ALK5), TGFBR2, TGIF1, THBS1, THBS2 Transcription Factors: CEBPB, JUN, MYC, NFKB1, SP1, STAT1, STAT6 Epithelial-to-Mesenchymal Transition: AKT1, BMP7, COL1A2, COL3A1, ILK, ITGAV, ITGB1, MMP2 (Gelatinase A), MMP3, MMP9, SERPINE1 (PAI-1), SMAD2, SNAI1 (Snail), TGFB1, TGFB2, TGFB3, TIMP1. Others: BCL2, FASLG (TNFSF6).
  • 26. Sample & Assay Technologies Oxidative Stress PCR Arrays http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-065Z.html Antioxidants: Glutathione Peroxidases (GPx): GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSTP1, GSTZ1. Peroxiredoxins (TPx): PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, PRDX6 (AOP2). Other Peroxidases: CAT, CYBB, CYGB, DUOX1, DUOX2, EPX, LPO, MGST3, MPO, PTGS1, PTGS2 (COX2), PXDN, TPO, TTN. Other Antioxidants: ALB, APOE, GSR, MT3, SELS, SOD1, SOD3, SRXN1, TXNRD1, TXNRD2. Genes Involved in Reactive Oxygen Species (ROS) Metabolism: Superoxide Dismutases (SOD): SOD1, SOD2, SOD3. Other Genes Involved in Superoxide Metabolism: ALOX12, CCS, DUOX1, DUOX2, GTF2I, MT3, NCF1, NCF2, NOS2 (iNOS), NOX4, NOX5, PREX1, UCP2. Other Genes Involved in ROS Metabolism: AOX1, BNIP3, EPHX2, MPV17, SFTPD. Oxidative Stress Responsive Genes: APOE, ATOX1, CAT, CCL5 (RANTES), CYGB, DHCR24, DUOX1, DUOX2, DUSP1 (PTPN16), EPX, FOXM1, FTH1, GCLC, GCLM, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, HMOX1, HSPA1A, KRT1, LPO, MBL2, MPO, MSRA, NQO1, NUDT1, OXR1, OXSR1, PDLIM1, PNKP, PRDX2, PRDX5, PRDX6 (AOP2), PRNP, RNF7, SCARA3, SELS, SEPP1, SIRT2, SOD1, SOD2, SQSTM1, SRXN1, STK25, TPO, TTN, TXN, TXNRD1, TXNRD2. Oxygen Transporters: CYGB, MB. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------- Joyce NC, Harris DL, Zhu CC. Age-related gene response of human corneal endothelium to oxidative stress and DNA damage. Invest Ophthalmol Vis Sci (2011) Mar 1;52(3):1641-9
  • 27. Sample & Assay Technologies Hypoxia PCR Arrays http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-032Z.html HIF1 & Co-Transcription Factors: ARNT, COPS5, HIF1A, HIF1AN, HIF3A, HNF4A, NCOA1, PER1. Other HIF1 Interactors: APEX1, EGLN1, EGLN2, NFKB1, P4HA1, P4HB, TP53. Responsive Genes: Angiogenesis: ADORA2B, ANGPTL4, ANXA2, BTG1, EGR1, EDN1, EPO, F3, GPI, HMOX1, JMJD6, LOX, MMP9, PGF, PLAU (uPA), SERPINE1 (PAI-1), VEGFA. Coagulation: ALDOA, ANXA2, F10, F3, F3, PLAU (uPA), SERPINE1 (PAI-1), SLC16A3. DNA Damage Signaling & Repair: ATR, MIF, NDRG1, RUVBL2. Metabolism: ALDOA, DDIT4 (REDD1), ENO1, ERO1L, GBE1, GPI, GYS1, HK2, LDHA, PDK1, PFKFB3, PFKFB4, PFKL, PFKP, PGAM1, PGK1, PKM2, SLC2A1, SLC2A3, TPI1. Regulation of Apoptosis: ADM, BNIP3, BNIP3L, BTG1, DDIT4 (REDD1), IER3, MIF, NOS3 (eNOS), PIM1. Regulation of Cell Proliferation: ADM, BTG1, BLM, CCNG2, EGR1, IGFBP3, MET, MIF, MXI1, NAMPT, NOS3 (eNOS), ODC1, PGF, PIM1, TXNIP. Transcription Factors: BHLHE40, FOS, RBPJ, USF2. Transporters, Channels & Receptors: SLC2A1, SLC2A3, SLC16A3, TFRC, VDAC1. Other Responsive Genes: ANKRD37, CA9, CTSA, DNAJC5, EIF4EBP1, LGALS3, MAP3K1. ------------------------------------------------------------------------------------------------------------------------------------------------------------------- Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci (2008) Sep 3;28(36):9055-65
  • 28. Sample & Assay Technologies NFκB Signaling or Targets PCR Arrays NFκB Signaling Pathway Plus PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-025Y.html NFκB Signaling Pathway PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-025Z.html NFκB Signaling Targets PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-225Z.html ------------------------------------------------------------------------------------------------------------- Fiume G, Vecchio E, De Laurentiis A, Trimboli F, Palmieri C, Pisano A, Falcone C, Pontoriero M, Rossi A, Scialdone A, Fasanella Masci F, Scala G, Quinto I. Human immunodeficiency virus-1 Tat activates NF-kappaB via physical interaction with IkappaB-alpha and p65. Nucleic Acids Res. 2011 Dec 19.
  • 29. Sample & Assay Technologies TGFβ Signaling or Targets PCR Arrays TGFβ / BMP Signaling Pathway Plus PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-035Y.html TGFβ / BMP Signaling Pathway PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-035Z.html TGFβ Signaling Targets PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-235Z.html ---------------------------------------------------------------------------------------------------------------- Garamszegi N, Garamszegi SP, Shehadeh LA, Scully SP. Extracellular matrix-induced gene expression in human breast cancer cells. Mol Cancer Res. (2009) Mar;7(3):319-29
  • 30. Sample & Assay Technologies Wnt Signaling or Targets PCR Arrays Wnt Signaling Pathway Plus PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-043Y.html Wnt Signaling Pathway PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-043Z.html Wnt Signaling Targets PCR Array: http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-243Z.html ---------------------------------------------------------------------------------------------------------------- Burkhalter RJ, Symowicz J, Hudson LG, Gottardi CJ, Stack MS. Integrin regulation of beta-catenin signaling in ovarian carcinoma. J Biol Chem. (2011) Jul 1;286(26):23467-75. Hussain M, Rao M, Humphries AE, Hong JA, Liu F, Yang M, Caragacianu D, Schrump DS. Tobacco smoke induces polycomb-mediated repression of Dickkopf-1 in lung cancer cells. Cancer Res. (2009) Apr 15;69(8):3570-8.
  • 31. Sample & Assay Technologies Contact Information Jesse Liang Email: jesse.liang@qiagen.com Technical Support: 1-888-503-3187 Email: support@sabiosciences.com Check Webinar Calendar: http://www.sabiosciences.com/seminarlist.php miRNA PCR Arrays: April 10, 17, 24 (Wednesdays) Mutation PCR Arrays: April 9 (Tuesday) Next Generation Sequencing (NGS): April 4,11,18 (Thursdays) Copy Number Variation PCR Arrays: April 25 (Thursday)