ABSTRACT
Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC) worldwide. Protein phosphatase 2A (PP2A) dysfunction has been widely reported in a broad range of malignancies due to its distinctive role in miscellaneous cellular processes. However, it is poorly understood whether aberrant alterations of PP2A are involved in the network of oncogenic events in LSCC. Here, we detected a panel of PP2A-associated proteins using western blot in both laryngeal squamous cell carcinoma tissues and paired adjacent normal tissues from patients (Data S1). We found that phospho-PP2A/C (Y307), α4, cancerous inhibitor of protein phosphatase 2A (CIP2A), Akt, ezrin, phospho-ezrin (T567), 14-3-3, and focal adhesion kinase (FAK) showed increased expression levels in carcinoma tissues relative to normal tissues, while phospho-Akt (T308) showed decreased levels. Our study, thus, provides a rationale for targeting PP2A to develop novel therapies and proposes a combination of interrelated biomarkers for the diagnostic evaluation and prognosis prediction in LSCC.
Subject(s)
Humans , Autoantigens/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Case-Control Studies , Cytoskeletal Proteins/metabolism , Focal Adhesion Kinase 1/metabolism , Gene Expression Profiling , Gene Expression Regulation , Gene Expression Regulation, Neoplastic , Intracellular Signaling Peptides and Proteins/metabolism , Laryngeal Neoplasms/metabolism , Larynx/metabolism , Membrane Proteins/metabolism , Phosphorylation , Protein Phosphatase 2/metabolismABSTRACT
PURPOSE: This study tried to identify novel gastric autoimmune antigens that might be involved in aggravating the atrophic gastritis among patients with Helicobacter pylori infection using two-dimensional immunoblotting analysis. MATERIALS AND METHODS: Proteins from gastric mucosal antrectomy specimens and AGS cells (gastric adenocarcinoma cell lines derived from a Caucasian patient who had received no prior therapy) were 2-dimensionally immunoblotted separately with a pool of 300 sera from H. pylroi-infected patients at Gyeongsang National University Hospital. RESULTS: Thirty-eight autoantigenic proteins including alcohol dehydrogenase [NADP+], alpha enolase, gastrokine-1, gastric triacylglycerol lipase, heat shock 70 kDa protein 1, and peroxiredoxin-2 were identified in the gastric mucosal tissue. Fourteen autoantigenic proteins including programmed cell death 6-interacting protein, serum albumin and T-complex protein 1 subunit gamma were identified in the AGS cells. Albumin, alpha-enolase, annexin A3, cytoplasmic actin 1, heat shock cognate 71 kDa protein and leukocyte elastase inhibitor were commonly observed autoantigenic proteins in both gastric mucosal tissue and AGS cells. Alpha-enolase, glutathione S-transferase P, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1, human mitochondrial adenosine triphosphate synthase (ATP) subunit beta, mitochondrial 60 kDa heat shock protein, peroxiredoxin-2, 78 kDa glucose-regulated protein precursor, tyrosine-protein phosphatase non-receptor type 11 and Tryptophan-Aspartic acid (WD) repeat-containing protein 1 showed 60% or higher amino acid positivity. CONCLUSION: These newly identified gastric autoimmune antigens might be useful in the control and prevention of gastroduodenal disorders, and might be valuable in breaking the vicious circle that exists in gastroduodenal disorders if their pathophysiological roles could be understood in the progress of chronic atrophic gastritis, gastroduodenal ulcers, intestinal metaplasia, and gastric carcinogenesis.
Subject(s)
Humans , Alcohol Dehydrogenase/metabolism , Autoantigens/metabolism , Electrophoresis, Gel, Two-Dimensional , Gastric Mucosa/metabolism , Helicobacter Infections/metabolism , Peptide Hormones/metabolism , Phosphopyruvate Hydratase/metabolismABSTRACT
Rheumatoid arthritis (RA) is a chronic inflammatiory disease that mainly destroys cartilages or bones at the joints. This inflammatory disorder is initiated by self-attack using own immune system, but the detail of pathological mechanism is unclear. Features of autoantigens leading to autoimmune disease are also under veil although several candidates including type II collagen have been suggested to play a role in pathogenesis. In this report, we tried to identify proteins responding to antibodies purified from RA patients and screen proteins up-regulated or down-regulated in RA using proteomic approach. Fibronectin, semaphorin 7A precursor, growth factor binding protein 7 (GRB7), and immunoglobulin mu chain were specifically associated with antibodies isolated from RA synovial fluids. In addition, some metabolic proteins such as adipocyte fatty acid binding protein, galectin-1 and apolipoprotein A1 precursor were overexpressed in RA synovium. Also, expression of peroxiredoxin 2 was up-regulated in RA. On the contrary, expression of vimentin was severely suppressed in RA synoviocytes. Such findings might give some insights into understanding of pathological mechanism in RA.
Subject(s)
Middle Aged , Male , Humans , Female , Aged , Adult , Synovial Fluid/metabolism , Sepharose/chemistry , Proteomics/methods , Inflammation , Gene Expression Regulation , Collagen Type II/biosynthesis , Autoantigens/metabolism , Arthritis, Rheumatoid/metabolismSubject(s)
Adolescent , Autoantibodies/analysis , Autoantigens/metabolism , Autoimmunity , Chemoprevention , Child , Female , Goiter, Endemic/enzymology , Humans , Hypothyroidism/enzymology , Iodide Peroxidase/metabolism , Iodine/deficiency , Iron-Binding Proteins/metabolism , National Health Programs , Prevalence , Sodium Chloride, Dietary/standards , Sri Lanka/epidemiology , Thyroglobulin/metabolismABSTRACT
Os autores utilizaram técnicas de imunofluorescência para estudar a topografia de proteínas Ro e La em células linfoblastóides sincronizadas de murinos utilizando soro humano mono-específico anti-Ro/SSA. Durante a fase S di cucki celular, o Ro/SSA foi visto como um salpicado grosso no núcleo e no citoplasma. Na fase M, o Ro/SSA apareceu no corpo celular como um padräo reticulado e ficou menos nítido na fase G1. Por outro lado, o La/SSB foi observado durante todo o ciclo celular. Na fase G1, o La/SSB foi visto no nucléolo; na fase S, no núcleo, como um padräo salpicado fino, e na fase M, o padräo salpicado permaneceu em todo o corpo celular. Essas observaçöes indicam que o Ro/SSA é expresso durante as diversas fases do ciclo celular e sugerem, ainda, a dependência celular desse antígeno