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

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 TGFβ and TNFα 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, TNFα 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 μM anti‐myc oligomer produces the same growth and differentiation effects as does 10 ng/ml TGFβ1. We conclude that downregulation of c‐myc expression represents a common mechanism of growth inhibition by TGFβ and TNFα, but that TNFα possesses an additional effect that is independent of c‐myc expression.