TGF‐β inhibits growth factor‐induced DNA synthesis in hamster fibroblasts without affecting the early mitogenic events

TGF‐β inhibits growth factor‐induced DNA synthesis in hamster fibroblasts without affecting the early mitogenic events
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TGF-β 抑制仓鼠成纤维细胞中生长因子诱导的 DNA 合成,而不影响早期有丝分裂事件

DOI:
10.1002/jcp.1041350114
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发表时间:
1988
影响因子:
5.6
通讯作者:
J. Pouysségur
J. Pouysségur
中科院分区:
生物学2区
文献类型:
--
作者:
J. Chambard;J. Pouysségur

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发现转化生长因子β(TGF-β)可抑制(IC 50 =0.1 ng/ml)α-凝血酶或FGF诱导的G 0阻滞中国仓鼠肺成纤维细胞促有丝分裂作用。生长因子刺激的细胞在其通过G 0/G1的进展过程中对TGF-β添加迅速变得不敏感,这表明促有丝分裂反应的早期步骤是TGF-β作用的靶点。令人惊讶的是,没有发现通常由生长因子触发的充分表征的早期促有丝分裂事件受到TGF-β添加的影响。这些答复包括:磷酸肌醇分解,蛋白激酶C的激活(通过EGF受体下调确定),随后pHi、c-fos和c-myc mRNA水平升高,核糖体蛋白S6磷酸化,RNA和蛋白质合成增加,鸟氨酸脱羧酶诱导。发现只有胸苷激酶(进入S期的标志物)的诱导被TGF-β抑制,当在G1早期加入TGF-β时抑制作用最大。这些结果表明,TGF-β的抑制作用不影响生长因子信号通路,但涉及与迄今分析的不同的早期事件。
Transforming growth factor beta (TGF‐β) was found to inhibit (IC50 =0.1 ng/ml) α‐thrombin or FGF‐induced mitogenicity in G0‐arrested Chinese hamster lung fibroblasts. Growth factor‐stimulated cells became rapidly insensitive to TGF‐β addition during their progression through G0/G1 suggesting that an early step of the mitogenic response was the target of TGF‐β action. Surprisingly, none of the well characterized early mitogenic events commonly triggered by growth factors was found to be affected by TGF‐β addition. These responses included: phosphoinositide breakdown, activation of protein kinase C as determined by EGF receptor down‐modulation, subsequent rises in pHi, c‐fos, and c‐myc mRNA levels, ribosomal protein S6 phosphorylation, the increase in RNA and protein synthesis, induction of ornithine decarboxylase. Only the induction of thymidine kinase, a marker of entry in the S phase, was found to be repressed by TGF‐β, with maximal inhibition when TGF‐β was added early in G1. These results indicate that the inhibitory action of TGF‐β does not affect the growth factors signalling pathways but touches an early event different from those so far analyzed.
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