Antisense inhibition of c-myc expression reveals common and distinct mechanisms of growth inhibition by TGFβ and TNFα

✍ Scribed by Cheryl Robinson-Benion; Kevin E. Salhany; Stephen R. Hann; Jeffrey T. Holt

• Book ID: 102877445
• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 655 KB
• Volume: 45
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240450210

✦ Synopsis

Downregulation of the c-myc gene in HL-60 cells is associated with growth inhibition and induction of differentiation. Previous studies have reported that the growth inhibitors TGFP and TNFa downregulate c-myc mRNA levels, suggesting the possibility that these agents may exert some of their phenotypic effects via c-myc downregulation. Our study demonstrates that although both growth inhibitors produce a similar decrease in c-myc protein synthesis, TNFa produces a greater growth inhibition and differentiation induction in HL-60 cells. Combined addition of anti-myc oligomer with either growth inhibitor produces no additive effect. In fact, 4 pM anti-myc oligomer produces the same growth and differentiation effects as does 10 ng/ml TGFPl . We conclude that downregulation of c-myc expression represents a common mechanism of growth inhibition by TCFP and TNFa, but that TNFa possesses an additional effect that is independent of c-myc expression.