ABSTRACT
Methylation pattern is presented here for first time as a potential molecular marker of changes on SSTR2A and SHP-1(I) gene promoter related to breast and prostate carcinoma. Our results have shown low concordances with SSTR2A and methylated state in prostate cancer and moderate relationship with unmethylated CpG-27 in breast cancer. We found significant concordances for both cancers and SHP-1(I) unmethylation, and increased HER2 expression and SSTR2A methylation in breast cancer. Moreover, we found a correlation between methylation patterns of two genes in normal breast tissue. These data might assist to select subgroups of patients for the administration of alternative therapies.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , DNA Methylation , Prostatic Neoplasms/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics , Receptors, Somatostatin/genetics , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Humans , Male , Middle Aged , Promoter Regions, Genetic , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Protein Isoforms , Receptors, Somatostatin/metabolismABSTRACT
It is well understood that helminth infections modulate the immune responses of their hosts but the mechanisms involved in this modulation are not fully known. Macrophages and dendritic cells appear to be consistently affected during this type of infection and are common target cells for helminth-derived molecules. In this report, we show that macrophages obtained from chronically Taenia crassiceps-infected mice displayed an impaired response to recombinant murine IFN-γ, but not to recombinant murine IL-4, as measured based on the phosphorylation of STAT1 and STAT6, respectively. These macrophages expressed high levels of SOCS3. However, the inhibition of phosphatase activity by orthovanadate restored the IFN-γ response of these macrophages by increasing STAT1 phosphorylation without affecting SOCS3 expression. Therefore, we aimed to identify the phosphatases associated with IFN-γ signaling inhibition and found that macrophages from T. crassiceps-infected mice displayed enhanced SHP-1 expression. Interestingly, the exposure of naïve macrophages to T. crassiceps excreted/secreted products similarly interfered with IFN-γ-induced STAT1 phosphorylation. Moreover, macrophages exposed to T. crassiceps excreted/secreted products expressed high levels of SOCS3 as well as SHP-1. Strikingly, human peripheral blood mononuclear cells that were exposed to T. crassiceps excreted/secreted products in vitro also displayed impaired STAT1 phosphorylation in response to IFN-γ; again, phosphatase inhibition abrogated the T. crassiceps excreted/secreted product-altered IFN-γ signaling. These data demonstrate a new mechanism by which helminth infection and the products derived during this infection target intracellular pathways to block the response to inflammatory cytokines such as IFN-γ in both murine and human cells.