Functional Disruption of IEX-1 Expression by Concatemeric Hammerhead Ribozymes Alters Growth Properties of 293 Cells

The early response gene IEX-1 modulates apoptosis and cell growth in a poorly defined fashion. Here, we describe the effect of hammerhead ribozymes specifically disrupting IEX-1 expression in 293 cells. Compared to vector control, 293 cells exhibit a reduced growth rate and a slowed cell cycle progression, when stably transfected with a concatemeric ribozyme construct. In addition, these 293 cells were much less sensitive to apoptosis induced by an activating Fas/CD95 antibody or by the anti-cancer drugs etoposide and doxorubicin. By modulating the cell cycle, IEX-1 might be part of a growth signal if favourable growth conditions prevail, whereas under unfavourable conditions, i.e. death receptor activation, IEX-1 facilitates apoptosis.