Ranganathan G, Getz M J
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905.
J Biol Chem. 1990 Feb 25;265(6):3001-4.
Transforming growth factor type beta 1 (TGF-beta 1) is a pleiotropic regulator of cell growth and differentiation which can potentiate or otherwise modify cellular responses to different growth factors such as epidermal growth factor (EGF). Since cellular responses to peptide growth factors are mediated, in part, through the regulation of specific gene expression, we have studied the effect of TGF-beta 1 on the EGF-dependent transcriptional of a diverse panel of genes which included the fibronectin gene, the cytoskeletal beta- and gamma-actin genes, and the c-fos protooncogene. The addition of a combination of TGF-beta 1 (10 ng/ml) and EGF (10 ng/ml) to quiescent AKR-2B cells maintained in serum-free medium resulted in a strong synergistic stimulation of transcription which was not evident using either growth factor individually at concentrations of 20-100 ng/ml. This effect was evident within 10 min and did not require the continual presence of TGF-beta 1 in the culture medium. Increased responsiveness of some gene promoters to EGF stimulation was evident for up to 6 h following a brief 10-min exposure to TGF-beta 1. Similar exposure to either platelet-derived growth factor or fibroblast growth factor had little or no effect on EGF-stimulated transcription. These results indicate that the transcriptional response of specific genes to EGF can be stably altered as a consequence of exposure to TGF-beta 1.
转化生长因子β1（TGF-β1）是细胞生长和分化的多效性调节因子，它可以增强或以其他方式改变细胞对不同生长因子（如表皮生长因子（EGF））的反应。由于细胞对肽生长因子的反应部分是通过特定基因表达的调节来介导的，我们研究了TGF-β1对多种基因的EGF依赖性转录的影响，这些基因包括纤连蛋白基因、细胞骨架β-肌动蛋白和γ-肌动蛋白基因以及c-fos原癌基因。将TGF-β1（10 ng/ml）和EGF（10 ng/ml）的组合添加到无血清培养基中培养的静止AKR-2B细胞中，会导致转录的强烈协同刺激，而单独使用浓度为20-100 ng/ml的任何一种生长因子时这种刺激并不明显。这种效应在10分钟内就很明显，并且不需要培养基中持续存在TGF-β1。在短暂暴露于TGF-β1 10分钟后的长达6小时内，一些基因启动子对EGF刺激的反应性增加很明显。类似地暴露于血小板衍生生长因子或成纤维细胞生长因子对EGF刺激的转录几乎没有影响。这些结果表明，由于暴露于TGF-β1，特定基因对EGF的转录反应可以被稳定改变。
