Analysis of polarity proteins expression in neoplastic processes associated with human Papillomavirus using organotypic cultures.

Abstract

Some Human Papillomavirus (HPV) types, known as high-risk HPV types, are etiologically associated with almost all cervical tumors and over 50% of other anogenital cancers. Infection by these viruses has been associated with alterations in cellular proliferation pattern in tissues, increased nucleus/cytoplasm ratio in infected epithelial cells and multiple genomic alterations in infected cells. These characteristics are common to the majority of cancers. High-risk HPV types express two oncoproteins, E6 and E7 that act on specific cellular factors promoting cell proliferation, favoring the loss of cellular polarity and promoting epithelium-mesenchyma transition. Several studies from our laboratories have shown that diverse cellular targets of the E6 protein are involved in the maintenance of cell polarity, including the human protein homologue of Drosophila tumor suppressor Disc Large (DLG1). This protein localizes to adherent intercellular junctions and has structural and signal transduction functions. E6 protein from high-risk HPV types binds DLG1 and induces it degradation through the ubiquitin-dependent proteolysis pathway. In fact, loss of DLG1 expression has been observed in high-grade lesions and cancers associated with HPV infection. Furthermore, other cellular adhesion proteins, including Scribble [adherent junctions], the Membrane-associated … (AU)