[The study on in vitro transformation by human papillomavirus type 16 E6/E7 region]

A NIH3T3-derived cell clone (NA7) in which human papillomavirus (HPV) 16 early region E6/E7 was inducible by dexamethasone (DXM) under the control of mouse mammary tumor virus long terminal repeat was established. A transforming function for HPV 16 E6/E7 region was analyzed by this established clone. Northern blot hybridization demonstrated that the increased expression of PCNA/cyclin and c-myc at the confluent state in accordance with the induced expression of E6/E7 region by DXM. Although complete transformation was not observed, the saturation density of NA7 was increased by the addition of DXM. The transfection assay using NA7 showed that adenovirus type 5 E1B (Ad5E1B) could cooperate with E6/E7. Furthermore, it was indicated that E7 could also cooperate with adenovirus type 5 E1B as well as with EJ-ras in transforming primary rat embryonal cells. However, E6/E7 could not cooperate with Ad12E1B in both cell systems. In this study, HPV 16 E6/E7 was assumed to have the growth-stimulatory activity in association with some cellular genes and transforming activity by cooperation with some transforming genes. These results suggest that E6/E7 seems to play a major role in the process of human cervical cell carcinogenesis.