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 poor ly defined fashion. Here, we describe the effect of hammerhead ribozymes sp ecifically disrupting IEX-1 expression in 293 cells, Compared to vector con trol, 293 cells exhibit a reduced growth rate and a slowed cell cycle progr ession, 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 anticancer drugs etoposide and do xorubicin, By modulating the cell cycle, IEX-1 might be part of a growth si gnal if favourable growth conditions prevail, whereas under unfavourable co nditions, i.e. death receptor activation, IEX-1 facilitates apoptosis, (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Sc ience B.V. All rights reserved.