Study of the action of bovine papillomavirus (BPV) in epithelial-mesenchymal transition

Abstract

Bovine papillomavirus (BPV) is the etiologic agent of bovine papillomatosis, infectious disease characterized by the presence of papillomas that regress spontaneously but can persist and progress to malignancy. The virus is considered the best model in understanding the oncogenic process of HPV. Studies suggest that papillomavirus induces epithelial-mesenchymal transition (EMT), which is characterized by morphological and transcriptional changes, conferring loss of cell adhesion and gain of motility. Although the association between papillomas and cancer has been known for more than 60 years, the mechanisms of malignant transformation, invasion and metastasis remain unknown. This work aims to evaluate the role of BPV in EMT in both cell culture and tissue samples (cutaneous papilloma tissue and esophageal carcinoma). Cutaneous papilloma, carcinoma of the esophagus and normal skin (control) cells will be cultured until passage six, evaluating the cell cycle by FACScan and the levels of clastogenicity by comet assay. The molecular diagnosis of BPV will be performed by PCR and sequencing. The expression of different markers of EMT, as well as the production of reactive oxygen species will be evaluated by FACScan and immunofluorescence. The migration and invasion assays will be used to assess cell motility. Samples from the same tissue that originated cell lines will be subjected to histopathological and immunohistochemical analysis using the same markers for EMT evaluated in vitro. (AU)