Loss of HPV-16 E7 dependence in cells transformed by HPV-16 E7 plus EJ-ras correlates with increased c-myc expression.

We have previously shown that continued expression of the HPV-16 E7 gene was required to maintain the transformed phenotype of primary baby rat kidney cells transformed by HPV-16 E7 plus EJ-ras. In this study we aimed to investigate the possible mechanisms by which cells could overcome this continued requirement for E7 expression. Using an inducible system for expression of the E7 gene we were able to generate cell lines no longer dependent on continued E7 expression. All such lines were still fully transformed, maintained inducible E7 expression and showed increased proliferative activity in the presence of HPV-16 E7 gene product. Further analysis has demonstrated a marked increase in the presence of c-myc protein in these cell lines when compared with the parental cells, suggesting a possible mechanism by which E7 dependence can be overcome.