Regulation of cell polarity proteins during the HPV infection

MARINA BUGNON VALDANO; A.L. CAVATORTA; F. MARZIALI; F. FACCIUTO; E. BOCCARDO; D. GARDIOL

Workshop; First ICGEB Workshop Human Papillomavirus: From Basic Biology to Cervical Cancer Prevention; 2014

Cell polarity depends on the asymmetric and highly regulated distribution of proteins and lipids. Loss of cell polarity and disruption of cell junctions is one of the main features of carcinogenic processes. We studied different mechanisms that regulate polarity proteins expression, considering carcinogenic processes associated to Human papillomaviruses (HPV) infections and malignant progression in general. We are focused on the DLG1 and PAR3 PDZ polarity proteins, having both structural and signaling functions. Their expression is altered in several tumors (in both oncovirus associated and independent tumors) but the mechanisms beyond these alterations remain unknown. By luciferase assays, we found that the DLG1 promoter activity is increased significantly in the presence of HPV E6 and/or E7 proteins in epithelial cells in culture (both for HPV of high or low oncogenic risk). Raft organotypic cultures reproduce epithelial differentiation in vitro and closely mimic the HPV-host interaction. Here we developed raft cultures expressing E6 and/or E7 HPV proteins. We analyzed the expression of known HPV cellular targets by Western Blot and Immunohistochemistry. DLG1 was found to be up-regulated and changed in its location in raft cultures expressing HPV E6 and E7. Also, we studied another HPV target: the cell polarity protein PAR3. We found that this protein is also highregulated and misdistributed in the presence of E6 and E7. Altogether, we have analyzed the expression of polarity cellular targets of HPV, in a context that closely resembles viral infections. These data suggest that the viral proteins could contribute to the changes in the cell proteins expression observed in biopsies.