ESTABLISHMENT OF AN APOPTOSIS-RESISTANT AND GROWTH-CONTROLLABLE CELL-LINE BY TRANSFECTING WITH INDUCIBLE ANTISENSE C-JUN GENE

F-MEL cells were transfected with the c-jun antisense gene located dow nstream of a glucocorticoid-inducible MMTV promoter, and the obtained cells were named c-jun AS cells. When the c-jun AS cells were treated with dexamethasone (DEX) in DMEM supplemented with 10% serum, the grow th of the cells was completely suppressed for a duration of 16 days wi th a high cell viability exceeding 86%. The c-jun expression in the c- jun AS cells was suppressed moderately in the absence of DEX and stron gly in the presence of DEX. The c-jun AS cells grew well and reached a density of 10(6) cells/mL without supplementation of any serum compon ents. Viability was greater than 80% after the cells had been cultured for 8 days in the absence of DEX. The c-jun AS cells stayed at a cons tant cell density and high viability above 80% for 8 days when they we re cultured in the presence of DEX under serum deprivation. In contras t, the wild type F-MEL cells were unable to grow and died by apoptosis in 3 days under serum deprivation. Internucleosomal cleavage of DNA, a landmark of apoptosis, was clearly detectable. Thus the c-jun AS cel l line that is resistant to apoptosis induced by serum deprivation and can reversibly and viably be growth-arrested was established. A dual- signal model was proposed to explain the experimental result, the inte rlinked regulation of apoptosis, and growth by c-jun. (C) 1998 John Wi ley & Sons, Inc.