Transforming growth factor beta regulation of epidermal growth factor receptor in ectocervical epithelial cells.
Transforming growth factor beta regulation of epidermal growth factor receptor in ectocervical epithelial cells.
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转化生长因子β对宫颈外上皮细胞表皮生长因子受体的调节。
DOI：
10.1006/excr.1995.1330
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发表时间：
1995
影响因子：
3.7
通讯作者：
Rorke,EA
中科院分区：
文献类型：
--
作者：
Jacobberger,JW;Sizemore,N;Gorodeski,G;Rorke,EA
转化生长因子β(转化生长因子β)是细胞功能的多能调节剂，是宫颈上皮细胞增殖的重要抑制因子。在本研究中，我们检测了转化生长因子β1对HPV16永生化宫颈上皮细胞中表皮生长因子受体水平和活性的影响。在ECE16-1细胞中，转化生长因子β-1处理后24小时内可观察到表皮生长因子受体水平的升高，并随时间的延长而持续升高。这种增加与转化生长因子β1依赖的增殖率下降有关。Scatchard分析表明，转化生长因子β-1诱导的表皮生长因子受体与受体的亲和力较低(Kd=4.08nM)，与转化生长因子β-1治疗前的受体亲和力(Kd=0.3nM和1.6nM)相比。转化生长因子β-1处理也降低了EGFRK的自磷酸化活性。细胞周期研究表明，经转化生长因子β1处理的细胞停滞于细胞周期的G1期，并且无论是经转化生长因子β1处理的细胞还是未处理的细胞，其对EGFR水平的调节都与细胞周期阶段无关。而EGFR水平与G1期时间相关。平行研究表明，转化生长因子β1依赖的p53水平的增加也与在G1中花费的时间增加相关。这些结果提示，转化生长因子β1对ECE16-1细胞增殖的抑制作用可能是通过将高亲和力/高活性的EGFR位点替换为低亲和力/低活性的EGFR位点，以及通过P53介导的细胞周期停滞来实现的。
Transforming growth factor β (TGFβ) is a pluripotent modulator of cell function and an important suppressor of cervical epithelial cell proliferation. In the present study, we examine the effects of TGFβ1 on the level and activity of the epidermal growth factor receptor (EGFR) in HPV-16 immortalized cervical epithelial cells. In ECE16-1 cells, increased EGFR levels are observed within 24 h after initiation of TGFβ1 treatment and levels continue to increase with time. This increase is correlated with a TGFβ1-dependent decrease in proliferation rate. Scatchard analysis indicates that the population of EGFR sites induced by TGFβ1 have a low affinity for EGF (Kd= 4.08 nM) compared to the receptors present prior to TGFβ1 treatment (Kd= 0.3 and 1.6 nM). TGFβ1 treatment also reduces EGFR kinase autophosphorylation activity. Cell cycle studies indicate that TGFβ1-treated cells arrest in the G1 phase of the cell cycle and that regulation of EGFR level was independent of cell cycle stage in both TGFβ1-treated and untreated cells. However, EGFR level was related to the G1 phase time. Parallel studies indicate that a TGFβ1-dependent increase in p53 level is also correlated with increased time spent in G1. These results suggest that TGFβ1 inhibition of ECE16-1 cell proliferation may act both by the replacement of high affinity/high kinase activity EGFR sites with low affinity/low kinase activity EGFR sites and a p53-mediated cell cycle arrest.