Cell and viral factors contributing to cell polarity disruption during HPV-associated carcinogenesis.

• FACCIUTO F, BUGNON VALDANO M, PANCERA B, NOCITO A, CAVATORTA AL, GARDIOL D

Tucumán

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2009

SAIB

E6 proteins derived from oncogenic HPV types have the ability to bind PDZ-domain containing proteins involved in control of cell polarity. Among them, human Disc large (DLG1) has been extensively studied and it was demonstrated to be lost in human tumours. We investigated the mechanisms regulating DLG1 expression and showed that Snail transcription factors repress the transcriptional activity of the DLG1 promoter and down-regulate DLG1 levels. Preliminary results indicate an inverse correlation between DLG1 and Snail expression in tumour biopsies, by optimizing an immunohistochemistry assay for Snail proteins. To further investigate the ability of HPV to disrupt polarity and tissue maintenance, we started to investigate how E6 proteins, through the binding to PDZ proteins, interfere with lipid distribution. This last point considering that the correct localization of phosphatidylinositol phosphates (PIP), in polarized cells, depends on the interaction with PDZ-containing proteins. We cloned E6 proteins derived from different HPV types, introduced them into epithelial cell lines and corroborated their proper cell distribution by immunofluorescence. The differences of PIP distribution in the presence or absence of E6 proteins is being analyzed through the localization of a PIP biosensor, the PH domain of phosholipase C fused to GFP, in stable cell lines expressing this construct.