ABSTRACT
Silencing of SOCS1 protein with shRNAi lentivirus (shR-SOCS1) led to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. SOCS1 silencing inhibited cell migration and invasion as well as in vitro growth by cell cycle arrest at S phase with increased cell size and nuclei. Down-regulation of SOCS1 decreased the expression of epidermal growth factor receptor, Ins-Rα, and fibroblast growth factor receptors. The present work aimed at analyzing the SOCS1 cell signaling and expression of proteins relevant to tumor development. An RNA microarray analysis of B16F10-Nex2 melanoma cells with SOCS1 silenced by shRNAi-SOCS1 was undertaken in comparison with cells transduced with the empty vector. Among 609 differentially expressed genes, c-Kit, Met and EphA3 cytokine/tyrosine-kinase (TK) receptors were down regulated. A significant decrease in the expression of TK receptors, the phosphorylation of mediators of ERK1/2 and p38 pathways and STAT3 (S727) were observed. Subcutaneous immunization with shR-SOCS1-transduced viable tumor cells rendered protection against melanoma in a syngeneic model, with decreased expression of PD-L1 and of matrix metallo-proteinases (MMPs) and CD-10 in those cells. The present work shows the role of SOCS1 in murine melanoma development and the potential of SOCS1-silenced tumor cells in raising an effective anti-melanoma immune response.
Subject(s)
B7-H1 Antigen/metabolism , Disease Progression , Epithelial-Mesenchymal Transition , Immunity , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Suppressor of Cytokine Signaling 1 Protein/metabolism , Animals , Bone Morphogenetic Protein Receptors, Type I/metabolism , Bone Morphogenetic Proteins/metabolism , CD8-Positive T-Lymphocytes/immunology , Cyclic AMP Response Element-Binding Protein/metabolism , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Gene Silencing , Melanoma, Experimental/genetics , Melanoma-Specific Antigens/metabolism , Mice, Inbred C57BL , NF-kappa B/metabolism , Protective Agents/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Signal Transduction , Smad Proteins/metabolism , Transcription Factor AP-2/metabolism , Transcription, Genetic , Transforming Growth Factor beta/metabolism , Tumor Microenvironment , Up-Regulation/geneticsABSTRACT
We studied the association of the mannose-binding lectin-2 (MBL2) polymorphism with anti-thyroid antibodies (ATA) in hepatitis C virus (HCV)-infected Brazilian patients (n = 162) and 124 healthy volunteers screened for ATA. Our results showed that patients with ATA had higher frequency of genotype 00 than controls. MBL may play a role as disease modifier in HCV infection.
Subject(s)
Autoimmunity/genetics , Hepacivirus/immunology , Hepatitis C/blood , Mannose-Binding Lectin/genetics , Polymorphism, Genetic , Thyroid Gland/immunology , Adolescent , Adult , Aged , Brazil , Case-Control Studies , Female , Hepatitis C/genetics , Humans , Male , Middle AgedABSTRACT
Em Escherichia coli, isoladas de infeccoes urinarias, foram detectadas diversas hemaglutininas (pili) manose-resistentes. A mais frequente delas associa-se ao sorogrupo 06, aglutinando apenas hemacias de carneiro
