Effects of protease inhibitors on c-myc expression in normal and transformed C3H 10T1/2 cell lines.
In the present study, the effect of protease inhibitors on c-myc expression in normal and transformed C3H 10T1/2 cells was examined. Steady-state c-myc RNA levels were reduced in normal proliferating C3H 10T1/2 cells grown in medium containing antipain, leupeptin, and Bowman Birk inhibitor (BBI). These protease inhibitors have been shown previously to suppress transformation yields in carcinogen-exposed cells. A lesser reduction in c-myc RNA levels was observed when cells were grown in the presence of protease inhibitors that do not suppress carcinogenesis and when transformed C3H 10T1/2 cell populations were grown in the presence of the anticarcinogenic protease inhibitors. Studies to determine the effects of antipain on the stability of the c-myc message and on c-myc transcription rates were also performed. The half-life of the c-myc message increased from 10 to 40 min when cells were grown in antipain; cycloheximide further stabilized the c-myc message. Interestingly, nuclear run-off experiments showed that antipain had no effect on c-myc transcription rates. These data suggest that proteases may be involved in the regulation of c-myc RNA expression in normal C3H 10T1/2 cells, possibly by a posttranscriptional mechanism.
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts.
J D
JD
Chang
J H
JH
Li
P C
PC
Billings
A R
AR
Kennedy
D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed; D051379:Mice; D008809:Mice, Inbred C3H; D009857:Oncogenes; D011480:Protease Inhibitors / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D014158:Transcription, Genetic
D011480:Protease Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA