emt and ecm 2013

Sample & Assay Technologies

EMT and ECM

Jesse Liang, Ph.D.

Sample & Assay Technologies Epithelial Cells

1. Closely adjoined2. Polarized

Epithelial Markers:E-Cadherin (adherens junctions)Claudins (tight junctions)Occludin (tight junctions)Desmoplakin (desmosomes)Cytokeratin-8, -18 and -19Mucin-1

There are 5 different types of cell junctions. They are tight junctions, adherens junctions, desmosomes, hemidesmosomes, and gap junctions.

Sample & Assay Technologies Mesenchymal Cells

1. Not adjoined2. No polarity

Mesenchymal Markers:VimentinN-CadherinFibronectinVitronectinFSP1(fibroblast-specific protein 1)Smooth-muscle actinFGFR2 IIIb and IIIc splice variants

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.

* Embryogenesis and development* Cancer * Fibrosis

Cell remodeling +

ECM remodeling

Sample & Assay Technologies The Nature of EMT

1. transient and reversible2. highly context-specific3. a vicious cycle in pathological conditions

Sample & Assay Technologies Activators and Suppressors of EMT

TGFβ, FGF, EGF families, HGF; Src, GTPase family – Ras, R ho, Rac; Snail, Slug, Twist, ZEB, NF κBExtracellular Cytoplasmic Nuclear

Epithelial-Mesenchymal Transitions in Development and Disease Cell (2009) 139, 871-890.

highly context-specific

Sample & Assay Technologies TGF-β and EMT & ECM

TGF-β is also one of the key cytokines in regulatingECM, not only by regulating expression of ECM structural proteins, but also by affecting enzymes involved in ECM biosynthesis and degradation.

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.

Sample & Assay Technologies EMT Signaling

Wilm’s tumor gene 1,In heart development

Oxygen-dependent gene expression indevelopment and cancer: lessons learned from the Wilm’s tumor gene, WT1.Front Mol Neurosci (2011), 4:1-11.

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.

Sample & Assay Technologies Induction of EMT Generates Stem-Like Cells

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.

Breast cancer – initiating cells are CD44+CD24- cells.

EMT phenotype EMT induction

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 miR-200a, and increases mammosphere forming ability in breast cancermiR-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 cancermiR-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 cancermiR-183 * ZEB1 represses miR-183 expression, which increases the expression of Bmi1 and KLF4 in pancreatic cancermiR-203* ZEB1 represses miR-203 expression, which increases the expression of Bmi1 and KLF4 in pancreatic cancer

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

Sample & Assay Technologies EMT and Fibrosis

Fibrosis is characterized by the presence of an excess offibrous 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).

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.

Sample & Assay Technologies Inflammation, Oxidative Stress and Hypoxia in EMT Induction

Inflammation and EMT: an alliance towards organ fibrosis and cancerprogression. EMBO Molecular Medicine (2009), 1, 303-314.

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

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.

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.

Sample & Assay Technologies EMT ChIP PCR Arrays – Profile Histone Codes

http://www.sabiosciences.com/chipqpcr_product/HTML/GH-090A.htmlGenes 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.

Sample & Assay Technologies miScript miRNA PCR Arrays

http://www.sabiosciences.com/mirna_pcr_array.php

miRNome (miRBase V19) Human Mouse Rat Dog Rhesus MacaquemiRNome (miRBase V19) 384 Well Human Mouse Rat Dog Rhesus MacaquemiFinder 96 Well Human Mouse Rat Dog Rhesus MacaquemiFinder 384 Well Human MouseApoptosis Human Mouse RatBrain Cancer Human Mouse RatBreast Cancer Human Mouse RatCancer PathwayFinder Human Mouse RatCardiovascular Disease Human Mouse RatDiabetes Human Mouse RatCell Differentiation & Development Human Mouse RatImmunopathology Human Mouse RatInflammatory Response and Autoimmunity Human Mouse RatNeurological Development & Disease Human Mouse RatOvarian Cancer Human Mouse RatProstate Cancer Human Mouse RatSerum & Plasma Human Mouse RatSerum & Plasma 384 Well HumanT-Cell & B-Cell Activation Human Mouse RatmiRNA QC Human Mouse Rat Dog Rhesus Macaque

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

Sample & Assay Technologies ECM (Extracellular Matrix) and Cell Adhesion PCR Arrays


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.

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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

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 Adhesionshttp://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-145Z.html

Tight Junctionshttp://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-143Z.html

Adherens Junctionshttp://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-146Z.html

Gap Junctionshttp://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-144Z.html

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

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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.

Sample & Assay Technologies Fibrosis PCR Arrays


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, THBS2Transcription Factors: CEBPB, JUN, MYC, NFKB1, SP1, STAT1, STAT6Epithelial-to-Mesenchymal Transition: AKT1, BMP7, COL1A2, COL3A1, ILK, ITGAV, ITGB1, MMP2 (GelatinaseA), MMP3, MMP9, SERPINE1 (PAI-1), SMAD2, SNAI1 (Snail), TGFB1, TGFB2, TGFB3, TIMP1.Others: BCL2, FASLG (TNFSF6).

Sample & Assay Technologies Oxidative Stress PCR Arrays


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) Met abolism: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.

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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

Sample & Assay Technologies Hypoxia PCR Arrays


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.

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Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci (2008) Sep 3;28(36):9055-65

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, ScalaG, Quinto I. Human immunodeficiency virus-1 Tat activates NF-kappaB via physical interaction with IkappaB-alpha and p65. Nucleic Acids Res. 2011 Dec 19.

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

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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

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.

Sample & Assay Technologies Contact Information

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Check Webinar Calendar:http://www.sabiosciences.com/seminarlist.phpmiRNA PCR Arrays: April 10, 17, 24 (Wednesdays) Mutation PCR Arrays: April 9 (Tuesday)Next Generation Sequencing (NGS): April 4,11,18 (Th ursdays)Copy Number Variation PCR Arrays: April 25 (Thursda y)

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