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.
Grobe
O
O
Laboratory of Molecular Gastroenterology, First Department of Internal Medicine, University of Kiel, Schittenhelmstr. 12, D-24105 Kiel, Germany.
Arlt
A
A
Ungefroren
H
H
Krupp
G
G
Fölsch
U R
UR
Schmidt
W E
WE
Schäfer
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013698:Templates, Genetic; D014162:Transfection; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D019014:fas Receptor; D005047:Etoposide; D004317:Doxorubicin