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. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company