Differential expression of the h-DLG oncosuppressor in histological samples from HPV-associated lesions as a marker for progression to malignancy.

CAVATORTA, ANA LAURA; FUMERO, GASTÓN; CHOUHY, DIEGO; AGUIRRE, ROXANA; NOCITO, ANA LIA; GIRI, ADRIANA A.; GARDIOL, DANIELA

San Carlos de Bariloche

Congreso; XXXIX Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2003

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

High risk HPVs play a causal role in the development of cervical cancer. HPV E6 oncoproteins target h-Dlg for ubiquitin-mediated proteolysis. h-Dlg oncosuppressor is associated with cell-cell interactions, and deregulation of these structures leads to defective cell adhesion, loss of cell polarity and unregulated proliferation. We evaluated the contribution of this E6 activity in the progression to malignancy in HPV infections by analyzing Dlg expression in HPV-associated lesions. We analyzed cervical, laryngeal, vulvar, colon and kidney histological samples by Dlg immunohistochemistry. HPV association was ascertained by a PCR-colorimetric method. Although Dlg was certainly expressed in the intraepithelial cervical, vulvar and laryngeal HPV associated lesions, its cellular and tissue distribution pattern was altered comparing with normal tissue. Interestingly, a critical reduction in Dlg levels was observed in HPV-positive cervical invasive carcinomas. However, Dlg loss was not observed in tumours not linked to HPV, such as colon and kidney carcinomas, even though changes in Dlg distribution archetype were detected. The loss of Dlg may be considered a late stage in cervical HPV carcinogenesis but alterations in its expression and localization take place during the different displastic stages.