Cotransfection of HPV-18 and v-fos DNA induces tumorigenicity of primary human keratinocytes.

Human keratinocytes were cotransfected with the FBJ/R v-fos oncogene and the HPV-18 genome and selected on the basis of their resistance to inducers of terminal differentiation. Unlike keratinocytes immortalized by HPV-18 DNA alone, the HPV-18/v-fos transformants exhibited prominent intracellular vacuolization and formed progressively growing, squamous cell tumors when injected subcutaneously into nude mice. Cytogenetic analysis of two clonally selected transformed cell lines (18/fos clone 1 and 18/fos clone 2) revealed minimal alterations in karyotype, although a consistent rearrangement of chromosome 10, iso(10q), was observed. Further analysis of 18/fos clone 1 confirmed the expression of the fos gene as well as the HPV-18 E7 protein. Alterations in fos gene expression, which appear to be an important facet of epidermal differentiation in vivo, could potentially contribute to the malignant progression of HPV immortalized cells.