Pring Miranda, Prime Stephen, Parkinson E Kenneth, Paterson Ian
Department of Oral and Dental Science, University of Bristol, Bristol BS1 2LY, UK.
Int J Oncol. 2006 May;28(5):1279-85.
This study examined Smad2- and Smad3-dependent transcription in 12 human head and neck squamous cell carcinoma (HNSCC) cell lines following treatment with transforming growth factor-beta1 (TGF-beta1). A markedly elevated level of TGF-beta1-induced Smad3 signalling was observed in one cell line (H357), whilst four cell lines (BICR31, H314, BICR56, BICR19) demonstrated absence of Smad3-dependent transcription that correlated with loss of TGF-beta1 growth inhibition; TGF-beta1-induced Smad2-dependent transcription was retained in two of these cell lines (H314, BICR31). Using transient expression of TGF-beta signalling components and a Smad3-dependent reporter assay, we show that BICR31 and H314 had defects of Smad4, BICR56 had abnormal TbetaR-II and BICR19 overexpressed Smad7. The results demonstrate that deregulated TGF-beta1-induced Smad signalling is common in HNSCC cell lines and can occur as a result of a variety of defects in the TGF-beta signal transduction pathway.
本研究检测了12种人头颈鳞状细胞癌（HNSCC）细胞系在转化生长因子-β1（TGF-β1）处理后Smad2和Smad3依赖性转录情况。在一种细胞系（H357）中观察到TGF-β1诱导的Smad3信号水平显著升高，而四种细胞系（BICR31、H314、BICR56、BICR19）显示缺乏Smad3依赖性转录，这与TGF-β1生长抑制作用丧失相关；TGF-β1诱导的Smad2依赖性转录在其中两种细胞系（H314、BICR31）中得以保留。通过TGF-β信号成分的瞬时表达和Smad3依赖性报告基因检测，我们发现BICR31和H314存在Smad4缺陷，BICR56存在异常的TβR-II，BICR19过表达Smad7。结果表明，TGF-β1诱导的Smad信号失调在HNSCC细胞系中很常见，并且可能是由于TGF-β信号转导途径中的多种缺陷所致。
