TUMOR NECROSIS FACTOR-INDUCED C-MYC EXPRESSION IN THE ABSENCE OF MITOGENESIS IS ASSOCIATED WITH INHIBITION OF ADIPOCYTE DIFFERENTIATION
TUMOR NECROSIS FACTOR-INDUCED C-MYC EXPRESSION IN THE ABSENCE OF MITOGENESIS IS ASSOCIATED WITH INHIBITION OF ADIPOCYTE DIFFERENTIATION
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DOI：
10.1073/pnas.90.20.9611
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发表时间：
1993-10-15
影响因子：
11.1
通讯作者：
RINGOLD, GM
中科院分区：
文献类型：
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作者：
NINOMIYATSUJI, J;TORTI, FM;RINGOLD, GM
肿瘤坏死因子抑制和逆转小鼠成脂细胞TA1的分化。我们发现，肿瘤坏死因子在前脂肪细胞和脂肪细胞中持续诱导c-myc；相反，血清只在前脂肪细胞中短暂地诱导c-myc。这种由肿瘤坏死因子介导的c-myc诱导与细胞增殖无关，但与肿瘤坏死因子介导的抑制脂肪细胞分化有关。我们在金属硫蛋白-I启动子的控制下，将小鼠c-myc基因导入TA1细胞，获得了可诱导的c-myc转化子。这些细胞在锌/镉存在的情况下不能分化为脂肪细胞，在分化的TA1细胞中，锌/镉导致脂肪细胞特异性基因表达的减少，肿瘤坏死因子也是如此。最后，TA1细胞暴露在反义c-myc寡核苷酸中，部分阻断了肿瘤坏死因子介导的脂肪细胞特异性基因表达的减少。因此，肿瘤坏死因子介导的c-myc表达在性质上不同于参与有丝分裂反应的c-myc表达，但似乎在抑制和逆转脂肪细胞分化方面发挥重要作用。
Tumor necrosis factor (TNF) inhibits and reverses differentiation of mouse adipogenic TA1 cells. We have found that TNF induces c-myc in a sustained manner in both preadipocytes and adipocytes; in contrast, serum induces c-myc transiently and only in preadipocytes. This TNF-mediated c-myc induction is not coupled with cell proliferation but is correlated with TNF-mediated inhibition of adipocyte differentiation. We prepared an inducible c-myc transformant of TA1 cells by transfection of the mouse c-myc gene under the control of the metallothionein-I promoter. These cells are unable to differentiate to adipocytes in the presence of Zn2+/Cd2+, and in differentiated TA1 cells, Zn2+/Cd2+ causes reduction of adipocyte-specific gene expression as does TNF. Lastly, exposure of TA1 cells to antisense c-myc oligonucleotide partially blocked the TNF-mediated reduction of adipocyte-specific gene expression. Thus, TNF-mediated c-myc expression is distinct in character from that involved in mitogenic responses but appears to play an important role in inhibition and reversal of adipocyte differentiation.