Deletion of the PDZ motif of HPV16 E6 preventing immortalization and anchorage-independent growth in human tonsil epithelial cells

Background. Human papillomavirus 16 (HPV16) has been associated with head and neck squamous cell carcinoma (HNSCC) in up to 60% of sampled specimens. Methods. To understand better the viral genes required to transform human tonsil epithelial cells (HTEC), we isolated HTECs and transduced them with retroviral vectors containing HPV16 E6 and E7. Results. Immortalization and anchorage-independent growth of HTECs only occurred with expression of E6 and E7 with resultant degradation of p53. However, cells expressing E6 lacking the PSD-95/disc-large/Zo-1 (PDZ) motif did not immortalize or grow anchorage independent. Telomerase activity and degradation of p53 were similar for wild-type and mutant E6. Conclusion. The mechanism of oncogenic transformation by E6 in HTECs is dependent on the PDZ binding motif. Identification of pathways affected by the interaction of E6 and PDZ domain containing proteins will further our understanding of how HPV causes HNSCC and will provide potential therapeutic targets.