Potentiated caspase-3 in Ras-transformed 10T1/2 cells.

Procaspase-3 protein content is highly elevated in fully Ras-transformed mouse embryo fibroblast 10T1/2 cells in which ectopic expression of oncogenic H-Ras is induced by a tetracycline-regulated expression system. Blockage of the ERK pathway results in profound reduction of transcript and protein content of procaspase-3 in both Ras-transformed and non-transformed counterpart 10T1/2 cells, indicating that the ERK pathway is involved in procaspase-3 gene expression. The elevated procaspase-3 protein content appears to facilitate the proteolytic production of active caspase-3 during selective induction of apoptosis of Ras-transformed cells by a discriminating anticancer agent, FR901228, whereas it induces growth arrest of non-transformed counterpart cells. The evidence indicates a potential role of the elevated procaspase-3 protein content and an essential role of the ERK pathway for procaspase-3 expression in the increased susceptibility of Ras-transformed 10T1/2 cells to anticancer agent FR901228.