A Cell Mutant That Exhibits Temperature-Dependent Sensitivity to Transformation by Various Oncogenes

Abstract

We previously isolated a Fisher rat fibroblast mutant, B812, that has the unique property of temperaturedependent transformation by various oncogenic retroviruses. At the permissive temperature (35°C), this mutant was sensitive to oncogenic transformation and formed foci on a dish at the same frequency as did the parental fibroblast cell line. When Kirsten murine sarcoma virus (Ki-MSV) was applied to the cells, the frequency of focus formation decreased more than 25-fold at the nonpermissive temperature (39°C), whereas the cells expressed nearly the same level of the ras transcript as well as the ras protein. The temperature- restricted focus formation was fully reversible and was completely suppressed upon fusion with the wild-type parent cell. In addition to ras, the mos, fos, src, and erbB-2 oncogenes transformed this mutant with the same temperature dependence as described above; polyomavirus middle T antigen, adenovirus type 12, and human papillomavirus 16-E67 also transformed, but without temperature dependence. These results suggest that ras, fos, mos, src, and erbB-2 use a common cellular pathway for transforming cells.