Aberrant Expression of Serpin Squamous Cell Carcinoma Antigen 2 in Human Tumor Tissues and Cell Lines: Evidence of Protection from Tumor Necrosis Factor-Mediated Apoptosis
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A. Takeda
Abstract
Squamous cell carcinoma antigens (SCCA) 1 and 2 are highly homologous proteins of the serpin family, although they inhibit different types of proteinases. We investigated the expression of both SCCA mRNAs in tumor tissues, in various cell lines (A431, SAS, Ca9, HeLa, SKGIIIa, HSC-2, HSC-3, HSC-4 and KB) and in HSC cell lines in the presence of tumor necrosis factor α (TNFα). The expression of SCCA2 mRNA could be differentiated from that of SCCA1 in tumor tissues and cell lines by means of reverse transcriptionpolymerase chain reaction (RTPCR). The ratio between SCCA1 and SCCA2 mRNA expression showed selective expression of SCCA2 mRNA in SCC tissues from the uterine cervix compared to SCC tissues from the esophagus or skin. In addition, a significant level of SCCA2 mRNA expression was detected in the HSC-4 cell line, but not in Ca9, HeLa, SKGIIIa, or HSC-3 cells. In contrast, SCCA1 mRNA was detected in all samples tested. These results suggest that the level of expression of SCCA2 mRNA detected by RTPCR can be used to evaluate the status of SCC tumors. Next, we studied the effect of TNFα on SCCA1 and SCCA2 mRNA expression in HSC cell lines. SCCA1 mRNA expression was constantly increased in the three HSC cells examined with increasing time of exposure to TNFα. In contrast, SCCA2 mRNA expression was specific for HSC-4 cells. The survival rate of HSC-4 cells pretreated with TNFα (6.3 ng/ml) for 48 h was found to be 72%, compared with 42% and 9% for HSC-3 and HSC-2 cells, respectively, after apoptotic stimulation by TNFα (10 ng/ml) and cycloheximide (10 g/ml) for 18 h. Furthermore, selective expression of SCCA2 mRNA in HSC-4 pretreated with TNFα protected these cells from TNFαmediated apoptosis. Thus, SCCA2 overexpression in squamous tumor cells contributed to their survival by protecting them against TNFαinduced apoptosis.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- The International Proteolysis Society (IPS): A Society for Proteolysis, Proteases and Protease Inhibitors
- Proteases and Their Inhibitors: Traditional Research Subjects in the Munich Area
- Apoptotic Pathways: Involvement of Lysosomal Proteases
- Human Tissue Kallikreins: A New Enzymatic Cascade Pathway?
- Discovery of Chemokine Substrates for Matrix Metalloproteinases by Exosite Scanning: A New Tool for Degradomics
- Novel Secretory Vesicle Serpins, Endopin 1 and Endopin 2: Endogenous Protease Inhibitors with Distinct Target Protease Specificities
- Extracellular Proteases of Staphylococcus spp.
- Secreted Aspartic Proteases as Virulence Factors of Candida Species
- Triple-Helical Peptide Analysis of Collagenolytic Protease Activity
- Phage Display Substrate: A Blind Method for Determining Protease Specificity
- Evolution of Placental Proteases
- Factor VII Activating Protease (FSAP): A Novel Protease in Hemostasis
- Cold-Adapted and Mesophilic Brachyurins
- The Role of Dipeptidyl Peptidase IV (DP IV) Enzymatic Activity in T Cell Activation and Autoimmunity
- Biochemical Features, Molecular Biology and Clinical Relevance of the Human 15-Domain Serine Proteinase Inhibitor LEKTI
- Interaction of Plasminogen Activator Inhibitor Type-1 (PAI-1) with Vitronectin (Vn): Mapping the Binding Sites on PAI-1 and Vn
- Structure-Function Relationship of Bromelain Isoinhibitors from Pineapple Stem
- Structural Basis for the Processive Protein Degradation by Tricorn Protease
- Zinc Ligands in an Astacin Family Metalloprotease Meprin A
- Probing the Active Sites and Mechanisms of Rat Metalloproteases Meprin A and B
- (R)-3-Amidinophenylalanine-Derived Inhibitors of Factor Xa with a Novel Active-Site Binding Mode
- Inhibition of Arginine Gingipains (RgpB and HRgpA) with Benzamidine Inhibitors: Zinc Increases Inhibitory Potency
- Cathepsin B Stability, But Not Activity, Is Affected in Cysteine:Cystine Redox Buffers
- Inhibition of Mammalian Legumain by Michael Acceptors and AzaAsn-Halomethylketones
- Role of the Prosegment of Fasciola hepatica Cathepsin L1 in Folding of the Catalytic Domain
- Roles for Arg- and Lys-Gingipains in the Disruption of Cytokine Responses and Loss of Viability of Human Endothelial Cells by Porphyromonas gingivalis Infection
- Aberrant Expression of Serpin Squamous Cell Carcinoma Antigen 2 in Human Tumor Tissues and Cell Lines: Evidence of Protection from Tumor Necrosis Factor-Mediated Apoptosis
- Endosomal-Lysosomal Proteolysis Mediates Death Signalling by TNFα, Not by Etoposide, in L929 Fibrosarcoma Cells: Evidence for an Active Role of Cathepsin D
- Anti-Inflammatory Effect of Pre-Elafin in Lipopolysaccharide-Induced Acute Lung Inflammation
- The 26S Proteasome Rpn10 Gene Encoding Splicing Isoforms: Evolutional Conservation of the Genomic Organization in Vertebrates
- Reverse Genetic Analysis of the Caenorhabditis elegans 26S Proteasome Subunits by RNA Interference
- Purification and Characterization of the 20S Proteasome from Ostrich Skeletal Muscle
- Identification of a Signal Transduction Pathway That Regulates MMP-9 mRNA Expression in Glomerular Injury
- Modulation of the Endosomal and Lysosomal Distribution of Cathepsins B, L and S in Human Monocytes/Macrophages
- Characterization of Novel Anti-Cathepsin W Antibodies and Cellular Distribution of Cathepsin W in the Gastrointestinal Tract
- Functional Consequences of Cathepsin L Deficiency in Human Lung Epithelial Cells
- Determination of Cathepsin B Expression May Offer Additional Prognostic Information for Ovarian Cancer Patients
- CA-074, But Not Its Methyl Ester CA-074Me, Is a Selective Inhibitor of Cathepsin B within Living Cells
- Trypsin Mutants for Structure-Based Drug Design: Expression, Refolding and Crystallisation