c-Jun Promotes whereas JunB Inhibits Epidermal Neoplasia

Slides:



Advertisements
Similar presentations
CD271 Mediates Stem Cells to Early Progeny Transition in Human Epidermis  Francesca Truzzi, Annalisa Saltari, Elisabetta Palazzo, Roberta Lotti, Tiziana.
Advertisements

The δ-Opioid Receptor Affects Epidermal Homeostasis via ERK-Dependent Inhibition of Transcription Factor POU2F3  Christine Neumann, Mei Bigliardi-Qi,
The Tumor Necrosis Factor Superfamily Molecule LIGHT Promotes Keratinocyte Activity and Skin Fibrosis  Rana Herro, Ricardo Da S. Antunes, Amelia R. Aguilera,
Yoshihisa Ishikawa, Masanori Kitamura  Kidney International 
Cdc42 Inhibits ERK-Mediated Collagenase-1 (MMP-1) Expression in Collagen-Activated Human Keratinocytes  Maryam G. Rohani, Brian K. Pilcher, Peter Chen,
KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage  Xiaoling Zhang, Suju Luo, Joseph Wu, Long Zhang, Wen-hui Wang,
Sarah A. Best, Amy N. Nwaobasi, Chrysalyne D. Schmults, Matthew R
Constitutive Phosphorylation of Focal Adhesion Kinase Is Involved in the Myofibroblast Differentiation of Scleroderma Fibroblasts  Yoshihiro Mimura, Hironobu.
Myung Jin Son, Kevin Woolard, Do-Hyun Nam, Jeongwu Lee, Howard A. Fine 
Inactivation of the Vitamin D Receptor Enhances Susceptibility of Murine Skin to UV- Induced Tumorigenesis  Tara I. Ellison, Molly K. Smith, Anita C. Gilliam,
Tamibarotene Ameliorates Bleomycin-Induced Dermal Fibrosis by Modulating Phenotypes of Fibroblasts, Endothelial Cells, and Immune Cells  Tetsuo Toyama,
Linda Vi, Stellar Boo, Samar Sayedyahossein, Randeep K
PTF1α/p48 and cell proliferation
Sarah A. Best, Amy N. Nwaobasi, Chrysalyne D. Schmults, Matthew R
Complement Factor H: A Biomarker for Progression of Cutaneous Squamous Cell Carcinoma  Pilvi M. Riihilä, Liisa M. Nissinen, Risto Ala-aho, Markku Kallajoki,
Masanori Ono, M. D. , Ph. D. , Ping Yin, Ph. D. , Antonia Navarro, M
Decreased Expression of Caveolin-1 Contributes to the Pathogenesis of Psoriasiform Dermatitis in Mice  Yukie Yamaguchi, Yuko Watanabe, Tomoya Watanabe,
Yasuyo Sano, Jin Mo Park  Journal of Investigative Dermatology 
Helium–Neon Laser Irradiation Stimulates Cell Proliferation through Photostimulatory Effects in Mitochondria  Wan-Ping Hu, Jeh-Jeng Wang, Chia-Li Yu,
CYLD Inhibits Melanoma Growth and Progression through Suppression of the JNK/AP-1 and β1-Integrin Signaling Pathways  Hengning Ke, Christina K. Augustine,
Naoko Kanda, Shinichi Watanabe  Journal of Investigative Dermatology 
RNA-Seq and ChIP-Seq Reveal SQSTM1/p62 as a Key Mediator of JunB Suppression of NF-κB-Dependent Inflammation  Xiaoling Zhang, Jane Y. Jin, Joseph Wu,
Conditional PDK1 Ablation Promotes Epidermal and T-Cell-Mediated Dysfunctions Leading to Inflammatory Skin Disease  Minjun Yu, David M. Owens, Sankar.
Tie2-R849W Mutant in Venous Malformations Chronically Activates a Functional STAT1 to Modulate Gene Expression  Hsiao-Tang Hu, Yi-Hsien Huang, Yi-Ann.
Enhancing Structural Support of the Dermal Microenvironment Activates Fibroblasts, Endothelial Cells, and Keratinocytes in Aged Human Skin In Vivo  Taihao.
Linda Vi, Stellar Boo, Samar Sayedyahossein, Randeep K
Ganna Bilousova, Jiang Chen, Dennis R. Roop 
CD271 Mediates Stem Cells to Early Progeny Transition in Human Epidermis  Francesca Truzzi, Annalisa Saltari, Elisabetta Palazzo, Roberta Lotti, Tiziana.
Matrix Metalloproteinase-21 Expression Is Associated with Keratinocyte Differentiation and Upregulated by Retinoic Acid in HaCaT Cells  Tiina Skoog, Outi.
Role of the Notch Ligand Delta1 in Embryonic and Adult Mouse Epidermis
Brian Poligone, Elaine S. Gilmore, Carolina V
Transcription Factor CTIP2 Maintains Hair Follicle Stem Cell Pool and Contributes to Altered Expression of LHX2 and NFATC1  Shreya Bhattacharya, Heather.
Mohammad Rashel, Ninche Alston, Soosan Ghazizadeh 
Absence of Distinguishing Senescence Traits in Human Melanocytic Nevi
Epidermal RelA Specifically Restricts Contact Allergen–Induced Inflammation and Apoptosis in Skin  Snehlata Kumari, Benjamin Herzberg, Ruth Pofahl, Thomas.
SIRT1 Activation Ameliorates Aldara-Induced Psoriasiform Phenotype and Histology in Mice  Sijing Xie, Zhonglan Su, Bin Zhang, Jiuyu Ge, Shiyu Song, Guibo.
Sustained Activation of Fibroblast Transforming Growth Factor-β/Smad Signaling in a Murine Model of Scleroderma  Shinsuke Takagawa, Gabriella Lakos, Yasuji.
Vitamin D Analog Calcipotriol Suppresses the Th17 Cytokine–Induced Proinflammatory S100 “Alarmins” Psoriasin (S100A7) and Koebnerisin (S100A15) in Psoriasis 
Discoidin Domain Receptor 2–microRNA 196a–Mediated Negative Feedback against Excess Type I Collagen Expression Is Impaired in Scleroderma Dermal Fibroblasts 
14-3-3σ Regulates Keratinocyte Proliferation and Differentiation by Modulating Yap1 Cellular Localization  Sumitha A.T. Sambandam, Ramesh B. Kasetti,
Keratinocyte-Specific Deletion of the Receptor RAGE Modulates the Kinetics of Skin Inflammation In Vivo  Julia S. Leibold, Astrid Riehl, Jan Hettinger,
Naoko Kanda, Shinichi Watanabe  Journal of Investigative Dermatology 
Leah C. Biggs, Lindsey Rhea, Brian C. Schutte, Martine Dunnwald 
Dual Role of the Anaphase Promoting Complex/Cyclosome in Regulating Stemness and Differentiation in Human Primary Keratinocytes  Ling Shih Quek, Nicolas.
Pituitary Tumor-Transforming Gene 1 Enhances Proliferation and Suppresses Early Differentiation of Keratinocytes  Yosuke Ishitsuka, Yasuhiro Kawachi,
Observations of Skin Grafts Derived from Keratinocytes Expressing Selectively Engineered Mutant Laminin-332 Molecules  Noriyasu Sakai, Elizabeth A. Waterman,
Epidermal Inactivation of the Glucocorticoid Receptor Triggers Skin Barrier Defects and Cutaneous Inflammation  Lisa M. Sevilla, Víctor Latorre, Ana Sanchis,
Role for Protein Kinase C-α in Keratinocyte Growth Arrest
Wnt1 Is Anti-Lymphangiogenic in a Melanoma Mouse Model
Nighat Yasmin, Sabine Konradi, Gregor Eisenwort, Yvonne M
Insulin-Like Growth Factor-Binding Protein 7 Regulates Keratinocyte Proliferation, Differentiation and Apoptosis  Janna Nousbeck, Ofer Sarig, Nili Avidan,
Increased Expression of Wnt2 and SFRP4 in Tsk Mouse Skin: Role of Wnt Signaling in Altered Dermal Fibrillin Deposition and Systemic Sclerosis  Julie Bayle,
Involvement of αvβ5 Integrin in the Establishment of Autocrine TGF-β Signaling in Dermal Fibroblasts Derived from Localized Scleroderma  Yoshihide Asano,
Jaana Mannik, Kamil Alzayady, Soosan Ghazizadeh 
Collagen Synthesis Is Suppressed in Dermal Fibroblasts by the Human Antimicrobial Peptide LL-37  Hyun Jeong Park, Dae Ho Cho, Hee Jung Kim, Jun Young.
Integrin-β4–TNS4–Focal Adhesion Kinase Signaling Mediates Keratinocyte Proliferation in Human Skin  Eun Young Seo, Seon-Pil Jin, Yeon Kyung Kim, Hanon.
PKCε Overexpression, Irrespective of Genetic Background, Sensitizes Skin to UVR- Induced Development of Squamous-Cell Carcinomas  Jordan M. Sand, Moammir.
Targeted Depletion of Polo-Like Kinase (Plk) 1 Through Lentiviral shRNA or a Small- Molecule Inhibitor Causes Mitotic Catastrophe and Induction of Apoptosis.
Transcriptional Repression of miR-34 Family Contributes to p63-Mediated Cell Cycle Progression in Epidermal Cells  Dario Antonini, Monia T. Russo, Laura.
Volume 125, Issue 4, Pages (May 2006)
TAK1 Is Required for Dermal Wound Healing and Homeostasis
IL-17A Upregulates Keratin 17 Expression in Keratinocytes through STAT1- and STAT3- Dependent Mechanisms  Xiaowei Shi, Liang Jin, Erle Dang, Ting Chang,
Protein Kinase C-Dependent Upregulation of miR-203 Induces the Differentiation of Human Keratinocytes  Enikö Sonkoly, Tianling Wei, Elizabeth Pavez Loriè,
All-Trans Retinoic Acid Antagonizes UV-Induced VEGF Production and Angiogenesis via the Inhibition of ERK Activation in Human Skin Keratinocytes  Mi-Sun.
Naoko Kanda, Shinichi Watanabe  Journal of Investigative Dermatology 
Involvement of PPARγ in Oxidative Stress-Mediated Prostaglandin E2 Production in SZ95 Human Sebaceous Gland Cells  Qiwei Zhang, Holger Seltmann, Christos.
Galectin-3 Protects Keratinocytes from UVB-Induced Apoptosis by Enhancing AKT Activation and Suppressing ERK Activation  Jun Saegusa, Daniel K. Hsu, Wei.
Yoshinori Aragane, Akira Maeda, Chang-Yi Cui, Tadashi Tezuka 
Roland Houben, Sonja Ortmann, Astrid Drasche, Jakob Troppmair, Marco J
Role and Regulation of STAT3 Phosphorylation at Ser727 in Melanocytes and Melanoma Cells  Masanobu Sakaguchi, Masahiro Oka, Tetsushi Iwasaki, Yasuo Fukami,
Presentation transcript:

c-Jun Promotes whereas JunB Inhibits Epidermal Neoplasia Jane Y. Jin, Hengning Ke, Russell P. Hall, Jennifer Y. Zhang  Journal of Investigative Dermatology  Volume 131, Issue 5, Pages 1149-1158 (May 2011) DOI: 10.1038/jid.2011.1 Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 c-Jun but not JunB is induced in human squamous cell carcinoma (SCC). (a, b) Immunostaining of (a) c-Jun and (b) JunB in normal human skin (NS) and representative patient SCC samples. c-Jun and JunB (orange); nuclei (blue, Hoechst 3342); scale bar=40μm. (c) Percentage of cells with positive nuclei staining for c-Jun and JunB in NS and SCC samples. The graph represents cell counts from 4 to 5 sections of NS or SCC + SD. (d) Immunoblotting for c-Jun, phosphorylated c-Jun (p-c-Jun), JunB, p-JunB, and actin with protein lysates isolated from human keratinocytes (KC), A431 SCC cells, NS, or 10 SCC samples. Semiquantitative densitometry was analyzed using Kodak imaging system (Rochester, NY) and the number shown below each band represents the relative reading units obtained by normalizing the reading of each band to that of actin of the same sample and then to the normalized number of keratinocytes or NS. Please note the samples shown in a, b, and d were from different patients. Journal of Investigative Dermatology 2011 131, 1149-1158DOI: (10.1038/jid.2011.1) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 JunB and c-Jun display opposite roles in Ras-driven epidermal neoplasia. (a) Histological appearances of 6-week-old skin grafts regenerated on severe combined immunodeficient (SCID) mice. Primary human keratinocytes were transduced to express genes as indicated on the upright corner of each image and then used for skin grafting. D, dermis; E, epidermal tissue; H&E, hematoxylin and eosin; M, muscle; V, blood vessel. Grafts (n=4–6) displayed 100% phenotypic penetrance. (b–e) Immunofluorescent staining for Ki-67, cytokeratin 8 (K8), vimentin, and filaggrin (orange); nuclei (blue, Hoechst 3342); scale bar=40μm. (f) Soft agar colony formation. A431 cells transduced for expression of LacZ control, JunB-ER, or c-Jun-ER were used for soft agar colony formation in the absence or presence of 100nM 4-hydroxy-tamoxifen (4-OHT). The average numbers of colonies from triplicate wells +SD are shown. Journal of Investigative Dermatology 2011 131, 1149-1158DOI: (10.1038/jid.2011.1) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Dominant-negative JunB mutant (DNJunB) promotes Ras-driven epidermal neoplasia. (a) Activator protein 1 (AP1) gene reporter assay. 293T cells were co-transfected with an AP1-luciferase gene reporter construct along with expression constructs encoding LacZ, c-Fos, DNJunB, or DNc-Jun. The graph represents means of relative luciferase reading units (RLU)+SD. (b) Histological appearances of skin grafts regenerated on severe combined immunodeficient (SCID) mice with primary human keratinocytes that have been transduced to express genes as indicated on the upper left corner of each image. D, dermis; E, epidermal tissue; H&E, hematoxylin and eosin; M, muscle; MKK7, mitogen-activated protein kinase kinase 7; V, blood vessel. Grafts (n=4–6) displayed 100% phenotypic penetrance. (c–f) Immunofluorescent staining for Ki-67, cytokeratin 8, vimentin, and filaggrin (orange); nuclei (blue, Hoechst 3342); scale bar=40μm. Journal of Investigative Dermatology 2011 131, 1149-1158DOI: (10.1038/jid.2011.1) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 JunB inhibits human epidermal cell growth and increases cell senescence. (a) Cell growth analysis. Primary human keratinocytes were transduced with retroviruses for expression of green fluorescent protein (GFP) or JunB and then plated in triplicates in separate or co-culture dishes. GFP-positive and GFP-negative cells were trypsinized and counted under microscope 72hours later. (b) Cell growth analysis. Keratinocytes transduced to express LacZ or JunB-ER were plated in triplicates in the presence of 4-hydroxytomoxifen (4-OHT) in a dose-response manner and then collected for cell counting 72hours later. (c) Cell senescence analysis. Mock-transduced control (Con) cells and cells expressing JunB-ER were treated with 100nM 4-OHT for 48hours and then processed for β-galactosidase staining (β-Gal, blue); scale bar=100μm. Inducible expression of JunB-ER was confirmed by immunoblotting with an antibody against ERα with actin for control. (d) Quantitative index of β-Gal-positive cells. (e) Cell cycle distribution analysis by flow cytometry of keratinocytes transduced to express GFP or JunB. (f) Immunofluorescent staining of the regenerated skin grafts with antibodies against cyclin D1, cyclin-dependent kinase 4 (CDK4), and p16 (orange); nuclei (blue, Hoechst 3342); scale bar=40μm. Graphs in a, b, d, and e represent the mean values+SD. Journal of Investigative Dermatology 2011 131, 1149-1158DOI: (10.1038/jid.2011.1) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions