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 HTEC's and transduced them with retroviral vectors containing HPV16 E6 and E7.


RESULTS
Immortalization and anchorage-independent growth of HTEC's 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.


CONCLUSIONS
The mechanism of oncogenic transformation by E6 in HTEC's 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.
Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa, USA.
William C
WC
Spanos
Jeremy
J
Geiger
Mary E
ME
Anderson
George F
GF
Harris
Aaron D
AD
Bossler
Russell B
RB
Smith
Aloysius J
AJ
Klingelhutz
John H
JH
Lee
D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004847:Epithelial Cells; D017353:Gene Deletion; D044404:Genomic Islands / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D054731:PDZ Domains; D014066:Palatine Tonsil / Q000166:cytology / Q000821:virology*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D044767:Ubiquitin-Protein Ligases