The role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC
The role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC
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DOI：
10.1016/j.otohns.2010.01.034
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发表时间：
2010-05-01
影响因子：
3.4
通讯作者：
John, Maie A. St.
中科院分区：
文献类型：
--
作者：
Dohadwala, Mariam;Wang, Guanyu;John, Maie A. St.
目的：确定ZEB1在炎症诱导的头颈部鳞状细胞癌（HNSCC）上皮-间质转化（EMT）中的作用。研究设计：分子生物学研究。采用实时定量逆转录酶聚合酶链反应（RT-PCR）、Western blot分析和人HNSCC组织切片的免疫组织化学染色来确定炎症如何影响转录抑制因子ZEB1。环境：一所学术医院实验室。对象和方法：采用RT-PCR检测相对ZEB1 RNA水平，并通过免疫组织化学染色原位评估人HNSCC组织切片的蛋白表达。结果：IL-1 β处理的HNSCC细胞系显示E-cadherin mRNA显著降低，转录抑制因子ZEB1 mRNA表达显著增加。通过染色质免疫沉淀试验（ChIP）确定，IL-1 β暴露导致ZEB1在染色质水平上的结合增强。通过人HNSCC组织切片的免疫组化染色原位证实ZEB1和E-cadherin呈负相关。结论：我们最近的研究表明，炎症介质是HNSCC中EMT的有效调节因子。这是首次报道ZEB1在HNSCC炎症诱导的EMT促进中的作用。这一新定义的E-cadherin在HNSCC中的转录调控途径对靶向化学预防和治疗具有重要意义。(C) 2010年美国耳鼻喉头颈外科学会基金会。版权所有。
OBJECTIVES: To determine the role of ZEB1 in the inflammation-induced promotion of the epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC).STUDY DESIGN: A molecular biology study. Real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining of human HNSCC tissue sections were used to determine how inflammation affects the transcriptional repressor, ZEB1.SETTING: An academic hospital laboratory.SUBJECTS AND METHODS: Relative ZEB1 RNA levels were determined by RT-PCR, and protein expression was evaluated in situ by immunohistochemical staining of human HNSCC tissue sections.RESULTS: IL-1 beta-treated HNSCC cell lines demonstrated a significant decrease in E-cadherin mRNA and an increase in the mRNA expression of the transcriptional repressor ZEB1. IL-1 beta exposure led to enhanced ZEB1 binding at the chromatin level, as determined by chromatin immunoprecipitation assays (ChIP). An inverse relationship between ZEB1 and E-cadherin was demonstrated in situ by immunohistochemical staining of human HNSCC tissue sections.CONCLUSIONS: Our recent investigations indicate that inflammatory mediators are potent regulators of EMT in HNSCC. This is the first report indicating the role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. This newly defined pathway for transcriptional regulation of E-cadherin in HNSCC has important implications for targeted chemoprevention and therapy. (C) 2010 American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved.