Antisense inhibition of c-myc expression reveals common and distinct mechanisms of growth inhibition by TGF beta and TNF alpha.

Robinson-Benion C, Salhany KE, Hann SR, Holt JT
J Cell Biochem. 1991 45 (2): 188-95

PMID: 2055946 · DOI:10.1002/jcb.240450210

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 TGF beta and TNF alpha 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, TNF alpha 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 microM anti-myc oligomer produces the same growth and differentiation effects as does 10 ng/ml TGF beta 1. We conclude that downregulation of c-myc expression represents a common mechanism of growth inhibition by TGF beta and TNF alpha, but that TNF alpha possesses an additional effect that is independent of c-myc expression.

MeSH Terms (14)

Cell Differentiation Cell Division Depression, Chemical Drug Interactions Gene Expression Regulation, Neoplastic Humans Leukemia, Promyelocytic, Acute Male Phenotype Proto-Oncogene Proteins c-myc RNA, Antisense Transforming Growth Factor beta Tumor Cells, Cultured Tumor Necrosis Factor-alpha

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