MUTATIONS IN THE LONG CONTROL REGION OF HUMAN PAPILLOMAVIRUS DNA IN ORAL-CANCER CELLS, AND THEIR FUNCTIONAL CONSEQUENCES

Oral cancers frequently contain DNA of human papillomavirus (HPV) type 16 or 18, hut the functional significance of this is unclear, A role for HPV in the progression of oral cancer would be more plausible if t he viral transforming genes were likely to he overexpressed in oral ca ncer cells, We therefore isolated and sequenced the long control regio n (LCR) of HPV-16 or HPV-18 from three oral cancer cell lines and two lines of HPV-16-immortalized oral keratinocytes, using PCR, The functi onal activity of each LCR was measured by cloning it into a luciferase expression vector, followed by transfection into both normal oral ker atinocytes and oral cancer cells, For comparison, the LCRs of the wild -type HPV-16 and HPV-18 were studied. Several mutations were found in the LCRs isolated from oral cancer cells and HPV-immortalized oral epi thelial cells, The promoter activity of the mutated LCRs was significa ntly higher than that of the equivalent wild-type LCRs in oral cancer cells that contained the same HPV type, These results imply that mutat ions in the LCR of HPVs in oral cancer could lead to increased express ion of HPV-transforming proteins, which might contribute to the carcin ogenic process.