TGF beta inhibits Go/S-phase transition in primary fibroblasts. Loss of response to the antigrowth effect of TGF beta is observed after immortalization.
TGF beta inhibits Go/S-phase transition in primary fibroblasts. Loss of response to the antigrowth effect of TGF beta is observed after immortalization.
复制标题
TGF beta 抑制原代成纤维细胞的 Go/S 相转变。
作者：
V. Sorrentino;S. Bandyopadhyay
转化生长因子β（TGF β）可通过阻止静止细胞重新进入细胞周期，在啮齿动物成纤维细胞的二次培养中作为负生长调节剂。虽然TGF β抑制血清诱导的从Go期到S期的转变，但它不抑制fos、myc和JE的诱导。活跃生长的细胞的增殖也被皮摩尔量的TGF β抑制。相反，几种已建立的细胞系不受TGF β抑制，并且在这些细胞系中，TGF β可引起静止细胞恢复增殖。这种对TGF β的抗性可以追溯到从衰老危机中出现的永生细胞的早期分裂，这表明正常成纤维细胞对TGF β的反应的改变与无限的增殖潜力同时发生。在5种已建立的细胞系中，TGF β诱导DNA合成之前，先诱导PDGF B链mRNA以及与细胞复制相关的其它mRNA，如fos、myc和JE。在衰老细胞中，这些基因中没有一个是单独由TGF β诱导的。这些结果表明，TGF β可以负调节正常衰老成纤维细胞的生长。在永生化后可以立即检测到对TGF β的反应性的改变，这可能有助于这些细胞的增殖潜力增加。
Transforming growth factor beta (TGF beta) may act as a negative growth regulator in secondary cultures of rodent fibroblasts by preventing quiescent cells from re-entering the cell cycle. Although TGF beta inhibits the serum induced transition from the Go to the S phase it does not inhibit induction of fos, myc, and JE. Actively growing cells are also inhibited in their proliferation by picomolar amounts of TGF beta. In contrast several established cell lines are not inhibited by TGF beta and in these it can cause quiescent cells to resume proliferation. This resistance to TGF beta can be traced back to the early divisions of immortal cells emerging from a senescence crisis, suggesting that alterations in the response of normal fibroblasts to TGF beta are concurrent with an unlimited proliferative potential. Induction of DNA synthesis by TGF beta is preceded in 5 established cell lines by induction of PDGF B chain mRNA as well as of other mRNAs associated with cell replication such as fos, myc, and JE. None of these genes is induced by TGF beta alone in presenescent cells. These results indicate that TGF beta can negatively regulate growth of normal presenescent fibroblasts. Alterations in the responsiveness to TGF beta can be detected immediately after immortalization which may contribute to the increased proliferative potential of these cells.