Verena N. Lorenz, Michael P. Schön, Cornelia S. Seitz

Slides:

Advertisements

Similar presentations

Alpha-Actinin 4 Is Associated with Cancer Cell Motility and Is a Potential Biomarker in Non–Small Cell Lung Cancer Ming-Chuan Wang, PhD, Ying-Hua Chang,

Advertisements

Nan-Hyung Kim, Ai-Young Lee Journal of Investigative Dermatology

Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome Xiao Li, MD, Liyan Wan, MD, Jian Geng, MD, Chin-Lee.

SiRNA Knockdown of Tissue Inhibitor of Metalloproteinase-1 in Keloid Fibroblasts Leads to Degradation of Collagen Type I Masayo Aoki, Koichi Miyake,

Stefanie Krenzer, Heike Peterziel, Cornelia Mauch, Sachiko I

A Signal Transduction Pathway from TGF-β1 to SKP2 via Akt1 and c-Myc and its Correlation with Progression in Human Melanoma Xuan Qu, Liangliang Shen,

Jasmine George, Minakshi Nihal, Chandra K

MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration Dongqing Li, X.I. Li, Aoxue Wang, Florian Meisgen, Andor.

Yongping Shao, Kaitlyn Le, Hanyin Cheng, Andrew E. Aplin

Resveratrol Targets Transforming Growth Factor-β2 Signaling to Block UV-Induced Tumor Progression Kwang Ho Kim, Jung Ho Back, Yucui Zhu, Josh Arbesman,

Sarah A. Best, Amy N. Nwaobasi, Chrysalyne D. Schmults, Matthew R

Interleukin-1β Interferes with Epidermal Homeostasis through Induction of Insulin Resistance: Implications for Psoriasis Pathogenesis Claudia Buerger,

Gene Expression Profiling of the Leading Edge of Cutaneous Squamous Cell Carcinoma: IL-24-Driven MMP-7 Hiroshi Mitsui, Mayte Suárez-Fariñas, Nicholas.

Inactivation of the Vitamin D Receptor Enhances Susceptibility of Murine Skin to UV- Induced Tumorigenesis Tara I. Ellison, Molly K. Smith, Anita C. Gilliam,

Transient Receptor Potential Vanilloid 4 (TRPV4) Is Downregulated in Keratinocytes in Human Non-Melanoma Skin Cancer Camilla Fusi, Serena Materazzi,

RAF Inhibition Overcomes Resistance to TRAIL-Induced Apoptosis in Melanoma Cells Anja Berger, Sandra-Annika Quast, Michael Plötz, Nicholas-Frederik Kuhn,

POF1B Localizes to Desmosomes and Regulates Cell Adhesion in Human Intestinal and Keratinocyte Cell Lines Arianna Crespi, Alessandra Bertoni, Ilaria.

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,

HPV Type 16 Infection Switches Keratinocytes from Apoptotic to Proliferative Fate under TWEAK/Fn14 Interaction Hong Cheng, Na Zhan, Dong Ding, Xiaoming.

Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome Xiao Li, MD, Liyan Wan, MD, Jian Geng, MD, Chin-Lee.

Alpha-Actinin 4 Is Associated with Cancer Cell Motility and Is a Potential Biomarker in Non–Small Cell Lung Cancer Ming-Chuan Wang, PhD, Ying-Hua Chang,

Glyoxalase I Is Differentially Expressed in Cutaneous Neoplasms and Contributes to the Progression of Squamous Cell Carcinoma Xiao-Yan Zou, Dong Ding,

Yes-Associated Protein Contributes to the Development of Human Cutaneous Squamous Cell Carcinoma via Activation of RAS Jinjing Jia, Changji Li, Suju.

IL-25 Enhances HSV-1 Replication by Inhibiting Filaggrin Expression, and Acts Synergistically with Th2 Cytokines to Enhance HSV-1 Replication Byung Eui.

Retinoic Acid Inhibits Downregulation of ΔNp63α Expression During Terminal Differentiation of Human Primary Keratinocytes Casimir Bamberger, Hartwig.

Smad4 Loss in Mouse Keratinocytes Leads to Increased Susceptibility to UV Carcinogenesis with Reduced Ercc1-Mediated DNA Repair Doyel Mitra, Pamela Fernandez,

Knockdown of Myosin Va Isoforms by RNAi as a Tool to Block Melanosome Transport in Primary Human Melanocytes Mireille Van Gele, Barbara Geusens, Anne-Marie.

Hypoxia Impairs Skin Myofibroblast Differentiation and Function

Upregulated RIP3 Expression Potentiates MLKL Phosphorylation–Mediated Programmed Necrosis in Toxic Epidermal Necrolysis Sue Kyung Kim, Woo-Jung Kim,

Spleen Tyrosine Kinase Mediates EGFR Signaling to Regulate Keratinocyte Terminal Differentiation Nan-Lin Wu, Duen-Yi Huang, Li-Fang Wang, Reiji Kannagi,

Verena N. Lorenz, Michael P. Schön, Cornelia S. Seitz

Estrogen Upregulates Slug to Enhance the Migration of Keratinocytes

TGF-β-Induced (TGFBI) Protein in Melanoma: A Signature of High Metastatic Potential Laura Lauden, Johan Siewiera, Wahid Boukouaci, Kiran Ramgolam, Samia.

RhoB Promotes Cancer Initiation by Protecting Keratinocytes from UVB-Induced Apoptosis but Limits Tumor Aggressiveness Nicolas Meyer, Alexis Peyret-Lacombe,

Matrix Metalloproteinase-21 Expression Is Associated with Keratinocyte Differentiation and Upregulated by Retinoic Acid in HaCaT Cells Tiina Skoog, Outi.

Enhanced Death Ligand-Induced Apoptosis in Cutaneous SCC Cells by Treatment with Diclofenac/Hyaluronic Acid Correlates with Downregulation of c-FLIP

Integrin β6-Deficient Mice Show Enhanced Keratinocyte Proliferation and Retarded Hair Follicle Regression after Depilation Yanshuang Xie, Kevin J. McElwee,

Brian Poligone, Elaine S. Gilmore, Carolina V

The Eumelanin Intermediate 5,6-Dihydroxyindole-2-Carboxylic Acid Is a Messenger in the Cross-Talk among Epidermal Cells Daniela Kovacs, Enrica Flori,

Selective Inhibition of p300 HAT Blocks Cell Cycle Progression, Induces Cellular Senescence, and Inhibits the DNA Damage Response in Melanoma Cells Gai.

Enrique C. Torchia, Lei Zhang, Aaron J. Huebner, Subrata Sen, Dennis R

C/EBPγ Regulates Wound Repair and EGF Receptor Signaling

Prolonged Activation of ERK Contributes to the Photorejuvenation Effect in Photodynamic Therapy in Human Dermal Fibroblasts Yong Hyun Jang, Gi-Bang Koo,

Calmodulin-Like Protein Upregulates Myosin-10 in Human Keratinocytes and Is Regulated during Epidermal Wound Healing In Vivo Richard D. Bennett, Amy.

SIRT1 Activation Ameliorates Aldara-Induced Psoriasiform Phenotype and Histology in Mice Sijing Xie, Zhonglan Su, Bin Zhang, Jiuyu Ge, Shiyu Song, Guibo.

Inhibition of CRM1-Mediated Nucleocytoplasmic Transport: Triggering Human Melanoma Cell Apoptosis by Perturbing Multiple Cellular Pathways Gaurav Pathria,

Sema4D, the Ligand for Plexin B1, Suppresses c-Met Activation and Migration and Promotes Melanocyte Survival and Growth Joanne Soong, Yulin Chen, Elina.

SiRNA Knockdown of Ribonucleotide Reductase Inhibits Melanoma Cell Line Proliferation Alone or Synergistically with Temozolomide Jonathan E. Zuckerman,

NADPH Oxidase 1 Overexpression Enhances Invasion via Matrix Metalloproteinase-2 and Epithelial–Mesenchymal Transition in Melanoma Cells Feng Liu, Angela.

Electrical Stimulation Enhances Epidermal Proliferation in Human Cutaneous Wounds by Modulating p53–SIVA1 Interaction Anil Sebastian, Syed A. Iqbal,

14-3-3σ Regulates Keratinocyte Proliferation and Differentiation by Modulating Yap1 Cellular Localization Sumitha A.T. Sambandam, Ramesh B. Kasetti,

Yabin Cheng, Guangdi Chen, Magdalena Martinka, Vincent Ho, Gang Li

Leah C. Biggs, Lindsey Rhea, Brian C. Schutte, Martine Dunnwald

Nrf2 Promotes Keratinocyte Proliferation in Psoriasis through Up-Regulation of Keratin 6, Keratin 16, and Keratin 17 Luting Yang, Xueli Fan, Tingting.

Role for Protein Kinase C-α in Keratinocyte Growth Arrest

YAP and TAZ Regulate Skin Wound Healing

Critical Role of Paxillin in Aging of Human Skin

Insulin-Like Growth Factor-Binding Protein 7 Regulates Keratinocyte Proliferation, Differentiation and Apoptosis Janna Nousbeck, Ofer Sarig, Nili Avidan,

Cornulin Is Induced in Psoriasis Lesions and Promotes Keratinocyte Proliferation via Phosphoinositide 3-Kinase/Akt Pathways Changji Li, Lei Xiao, Jinjing.

MicroRNA-203 Regulates Melanosome Transport and Tyrosinase Expression in Melanoma Cells by Targeting Kinesin Superfamily Protein 5b Shunsuke Noguchi,

Jasmine George, Minakshi Nihal, Chandra K

Targeted Depletion of Polo-Like Kinase (Plk) 1 Through Lentiviral shRNA or a Small- Molecule Inhibitor Causes Mitotic Catastrophe and Induction of Apoptosis.

Anna Flammiger, Robert Besch, Anthony L. Cook, Tanja Maier, Richard A

Transcriptional Repression of miR-34 Family Contributes to p63-Mediated Cell Cycle Progression in Epidermal Cells Dario Antonini, Monia T. Russo, Laura.

Nan-Hyung Kim, Ai-Young Lee Journal of Investigative Dermatology

IL-17A Upregulates Keratin 17 Expression in Keratinocytes through STAT1- and STAT3- Dependent Mechanisms Xiaowei Shi, Liang Jin, Erle Dang, Ting Chang,

RXRα Ablation in Epidermal Keratinocytes Enhances UVR-Induced DNA Damage, Apoptosis, and Proliferation of Keratinocytes and Melanocytes Zhixing Wang,

Requirement of Dynactin p150Glued Subunit for the Functional Integrity of the Keratinocyte Microparasol H. Randolph Byers, Sarah G. Dykstra, Sandrine.

Aldo-Keto Reductase 1C3 Is Expressed in Differentiated Human Epidermis, Affects Keratinocyte Differentiation, and Is Upregulated in Atopic Dermatitis

Presentation transcript:

c-Rel Downregulation Affects Cell Cycle Progression of Human Keratinocytes Verena N. Lorenz, Michael P. Schön, Cornelia S. Seitz Journal of Investigative Dermatology Volume 134, Issue 2, Pages 415-422 (February 2014) DOI: 10.1038/jid.2013.315 Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Expression of c-Rel in squamous cell carcinoma (SCC). (a) Staining of c-Rel in paraffin-embedded tissue of normal skin, (b) invasive SCC, and (c and d) Bowen’s disease. Note positive c-Rel staining of (d, arrows) mitotic figures. (a–c) Bar=250 μm; (d) bar=125 μm. (e) Quantitative analysis of c-Rel staining in normal epidermis (NL), actinic keratosis (AK), Bowen’s disease (BD), and invasive SCC; error bars are ±SD; ***P<0.001. Journal of Investigative Dermatology 2014 134, 415-422DOI: (10.1038/jid.2013.315) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Downregulation of c-Rel leads to growth arrest and increase of apoptosis in HaCaT keratinocytes. (a) Western blotting of c-Rel in control (ctrl) and c-Rel small interfering RNA (siRNA)–transfected cells after 72 hours. (b) Phase-contrast photographs 72 hours after transfection. Bar=100 μm. (c) Growth curve of control siRNA (dashed line) and c-Rel siRNA cells (continuous line) from 24 hours until 96 hours after transfection. At least six microscopic fields (original magnification, × 160) were evaluated. (d) MTT-based proliferation assay 72 hours after siRNA transfection. (e) BrdU proliferation assay 72 hours after transfection showing significant inhibition of proliferation in c-Rel-downregulated HaCaT cells. (f) Apoptosis assay 72 hours after transfection. For all experiments: one representative of three independent experiments is shown, each experiment was performed in triplicates; error bars are ±SD; ***P<0.001, **P<0.01, *P<0.05. Ctrl, control. Journal of Investigative Dermatology 2014 134, 415-422DOI: (10.1038/jid.2013.315) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 c-Rel downregulation leads to an increased number of HaCaT cells in the G2/M phase and induces phosphorylated-histone H3Ser10 (p-H3Ser10) expression. (a) Cell cycle phase distribution of cells determined by FACS analysis. (b) Cell cycle phase distribution of vital control (gray) and c-Rel (black) small interfering RNA (siRNA) cells of four independent experiments. (c) Western blotting of G1/S and G2/M regulatory proteins for control (ctrl) and c-Rel siRNA-transfected HaCaT cells. (d) Digitally enhanced p-H3Ser10 immunofluorescence staining of cells counterstained with 4′,6-diamidino-2-phenylindole. Bar=50 μm. (e) Evaluation of p-H3Ser10–positive cell portion of cells 72 hours after transfection. At least 10 microscopic fields (original magnification, × 100) were evaluated. Two independent experiments yielded similar results. For all evaluations, error bars are ±SD; **P<0.01, *P<0.05. Ctrl, control. Journal of Investigative Dermatology 2014 134, 415-422DOI: (10.1038/jid.2013.315) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 c-Rel silencing causes increased mitotic cells as well as aberrant mitotic spindle formation. (a) Photographs of control (ctrl) and c-Rel knockdown cells stained for β-tubulin 72 hours after transfection. Arrows indicate aberrant mitotic spindles classified as monopolar, and arrowheads show bipolar abnormal mitotic spindles. Bar=20 μm. (b) Evaluation of abnormal spindle formation of control (ctrl) and c-Rel small interfering RNA (siRNA)–transfected cells 72 hours after transfection. Classification of spindle morphology based on immunofluorescence findings. One of two similar evaluations is shown here. (c) Evaluation of aberrant mitotic spindle portion of ctrl and c-Rel siRNA cells subdivided into mono-, bi-, or multipolar spindle morphology. Classification based on immunofluorescence findings. One representative of three independent experiments is shown, and at least 19 microscopic fields were evaluated; error bars are ±SD; ***P<0.001, **P<0.01. (d) Western blotting of aurora A and phospho-aurora AThr288 (p-aurora AThr288) for ctrl and c-Rel siRNA-transfected HaCaT cells. (e) Double immunostaining of control and c-Rel knockdown cells for β-tubulin and p-aurora AThr288. Bottom row shows merged picture with β-tubulin, p-aurora AThr288, and 4′,6-diamidino-2-phenylindole (blue). Bar=20 μm. Ctrl, control. Journal of Investigative Dermatology 2014 134, 415-422DOI: (10.1038/jid.2013.315) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions