Antisense inhibition of c-myc expression reveals common and distinct mechanisms of growth inhibition by TGF beta and TNF alpha.
Antisense inhibition of c-myc expression reveals common and distinct mechanisms of growth inhibition by TGF beta and TNF alpha.
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c-myc 表达的反义抑制揭示了 TGF β 和 TNF α 抑制生长的常见且独特的机制。
DOI：
10.1002/jcb.240450210
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发表时间：
1991
影响因子：
4
通讯作者：
Holt,JT
中科院分区：
文献类型：
--
作者：
Robinson-Benion,C;Salhany,KE;Hann,SR;Holt,JT
C-myc基因在HL-60细胞中的下调与生长抑制和诱导分化有关。已有研究报道，生长抑制剂转化生长因子β和肿瘤坏死因子α下调c-myc基因表达，提示这些药物可能通过下调c-myc而发挥其表型效应。我们的研究表明，虽然两种生长抑制剂对c-myc蛋白合成的抑制作用相似，但肿瘤坏死因子α对HL-60细胞的生长抑制和分化诱导作用更强。将抗myc寡聚体与任何一种生长抑制物联合加入，不会产生相加效应。事实上，4-μ-M反义寡聚体的生长分化作用与10 ng/mlTGF-β-1相同。我们认为，c-myc表达下调是转化生长因子β和肿瘤坏死因子α抑制细胞生长的共同机制，但肿瘤坏死因子α具有不依赖于c-myc表达的额外作用。
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.