Transformation and stimulation of DNA synthesis in NIH-3T3 cells are a titratable function of normal p21N-ras...

A plasmid has been constructed which contains the normal human N-ras proto-oncogene under the transcriptional control of the steroid-sensitive promoter of the mouse mammary tumor virus long terminal repeat. This plasmid has been introduced into NIH-3T3 cells producing a clone of cells, T15, which is phenotypically normal in the absence of the transcription inducer, dexamethasone, and transformed when treated with high levels of the inducer. At lower levels of dexamethasone, both morphological transformation and stimulation of DNA synthesis are titratable functions of p21N-ras levels. T15 cells have been used to demonstrate that: (i) a 20- to 50-fold over-expression of normal p21ras is required for complete cellular transformation, (ii) p21N-ras expression induces DNA synthesis and the effect can be amplified by epidermal growth factor, (iii) moderate increases in normal p21ras expression can influence cell behaviour.