Differential induction of transcription of c-myc and c-fos proto-oncogenes by 12-O-tetradecanoylphorbol-13-acetate in mortal and immortal human urothelial cells.

The effect of the skin tumor-promoter TPA (12-O-tetradecanoylphorbol-13-acetate) on expression of cellular proto-oncogenes has been examined in cell lines derived from human urothelium. A single treatment with TPA (1 microgram/ml) increased the transcription of c-fos and c-myc proto-oncogenes at least 20-fold in the mortal cell line HU 1752. The induction was transient and was accompanied by a rapid but transient change in cell morphology. When immortalized cell lines were treated with TPA a similar rapid and transient morphological response was observed, but the TPA treatment only increased the level of c-fos mRNA, suggesting that the normal regulation of c-myc transcription is altered in immortalized cells irrespective of their tumorigenic properties. The levels of c-Ha-ras and c-Ki-ras mRNAs were unaffected by TPA treatment in all cell lines.