RESUMO
The Notch pathway is a conserved signaling pathway and a form of direct cell-cell communication related to many biological processes during development and adulthood. Deregulation of the Notch pathway is involved in many diseases, including cancer. Almost 20% of all cancer cases have an infectious etiology, with viruses responsible for at least 1.5 million new cancer cases per year. Seven groups of viruses have been classified as oncogenic: hepatitis B and C viruses (HBV and HCV respectively), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), human T lymphotropic virus (HTLV-1), human papillomavirus (HPV), and Merkel cell polyomavirus (MCPyV). These viruses share the ability to manipulate a variety of cell pathways that are critical in proliferation and differentiation, leading to malignant transformation. Viral proteins interact directly or indirectly with different members of the Notch pathway, altering their normal function. This review focuses exclusively on the direct interactions of viral oncoproteins with Notch elements, providing a deeper understanding of the dual behavior of the Notch pathway as activator or suppressor of neoplasia in virus-related cancers.
Assuntos
Transformação Celular Neoplásica/metabolismo , Transformação Celular Viral , Vírus Oncogênicos/fisiologia , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Biomarcadores , Suscetibilidade a Doenças , Humanos , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Ligação Proteica , Receptores Notch/químicaRESUMO
OBJECTIVE: The aim of the present study was to evaluate differences in expression levels and localization status of PTEN, p53 and hDlg suppressor proteins in premalignant lesions and cervical cancer, and to analyze the possible correlation between them. METHODS: Expression levels (positivity/intensity) and localization (nuclear, membrane or cytoplasmic) of PTEN, hDlg and p53 were analyzed by immunohistochemistry in 43 cases with different stages of cervical intraepithelial neoplasia (CIN) and 105 invasive cervical carcinomas (ICC) (91 squamous carcinoma, 14 adenocarcinoma). Differences between proportions were evaluated. RESULTS: We found a decreased expression of PTEN in ICC that correlated with a loss of hDlg from the cell membrane. In contrast, no changes were found in p53 protein levels or localization in CIN and ICC. CONCLUSIONS: These results suggest that the abnormal expression and localization of PTEN during cervical carcinogenesis may be a consequence of modifications in the expression patterns of hDlg.