Overexpression of transforming growth factor β1 in head and neck epithelia results in inflammation, angiogenesis, and epithelial hyperproliferation
Overexpression of transforming growth factor β1 in head and neck epithelia results in inflammation, angiogenesis, and epithelial hyperproliferation
复制标题
DOI：
10.1158/0008-5472.can-04-1032
复制
发表时间：
2004-07-01
期刊：
影响因子：
11.2
通讯作者：
Wang, XJ
中科院分区：
文献类型：
--
作者：
Lu, SL;Reh, D;Wang, XJ
在本研究中，我们发现与正常头颈部组织相比，转化生长因子β1（TGF-β1）在人头颈部鳞状细胞癌（HNSCC）及其邻近组织中频繁过度表达。为了确定 TGF-β1 过表达在 HNSCC 癌变中的作用，我们培育了转基因小鼠，其中可以在头颈部上皮细胞中诱导 TGF-β1 转基因表达。头颈部上皮细胞中 TGF-β1 转基因诱导的水平与人类 HNSCC 中的水平相似，会引起严重的炎症和血管生成。因此，TGF-β1 转基因上皮表现出过度增殖。这些表型与转基因上皮和基质中增强的 Smad 信号传导相关。我们的研究表明，HNSCC 形成早期阶段的 TGF-β1 过度表达提供了促进肿瘤生长的微环境。
In the present study, we show that transforming growth factor beta1 (TGF-beta1) was frequently overexpressed in human head and neck squamous cell carcinomas (HNSCCs) and adjacent tissues in comparison with normal head and neck tissues. To determine the role of TGF-beta1 overexpression in HNSCC carcinogenesis, we generated transgenic mice in which TGF-beta1 transgene expression can be induced in head and neck epithelia. TGF-beta1 transgene induction in head and neck epithelia, at levels similar to those in human HNSCCs, caused severe inflammation and angiogenesis. Consequently, TGF-beta1-transgenic epithelia exhibited hyperproliferation. These phenotypes correlated with enhanced Smad signaling in transgenic epithelia and stroma. Our study suggests that TGF-beta1 overexpression at early stages of HNSCC formation provides a tumor promoting microenvironment.