Suppression of viral transformation in rat embryo fibroblast cells immortalized with transforming genes of human papillomavirus type 16.

The E6 and E7 genes of human papillomavirus type 16 (HPV16) immortalize rat primary embryo fibroblast cells (REF) but do not transform them, irrespective of the expressions of the two genes. Previously, we reported that REF cells suppress the transformed phenotypes of a rat cell line transformed by the E6 and E7 genes of HPV16 in somatic hybrid cells. REF cells immortalized by HPV16 E6E7 genes (671 cells) also retained the ability to suppress E6E7-mediated transformation. Transformation of 671 cells by retroviruses containing middle T of polyomavirus, v-K-ras, or v-mos was also suppressed. 671 cells infected with retrovirus having middle T of polyomavirus (PyMLV) expressed sufficient middle T protein to transform a rat cell line. Cell fusion experiments showed that 671 cells suppressed transformation by middle T of polyomavirus without affecting the expression of middle T. These results suggest that REF cells immortalized by HPV16 E6E7 genes possess an intracellular function that suppresses transformation not only by E6E7 genes but also by other viral oncogenes including middle T of polyomavirus.