ATF3在砷致支气管上皮细胞损伤、恶性转化和EMT中的作用及机制

ATF3是含亮氨酸拉链结构的转录因子，可被多种应激因子激活。ATF3表达水平与多种肿瘤的发生发展和侵袭转移有关，但机制尚未阐明。本课题组预实验发现，砷可上调ATF3在人支气管上皮细胞（BEAS-2B）中的表达，且ATF3上调对CDC25A、GADD45α和Egr-1的表达有调控作用。本项目将建立高浓度砷引起BEAS-2B细胞损伤模型和低浓度砷诱导BEAS-2B细胞恶性转化模型，应用反义技术、分子生物学手段等，揭示ATF3对砷致支气管上皮细胞损伤、恶性转化和上皮间质转化（EMT）的作用，探究ATF3对砷致肺癌的抑制作用及机制，为发展ATF3为砷致肺癌预防、治疗及预后的靶点提供依据。

ATF3 is a transcription factor that contains a basic-region leucine zipper (bZIP) domain and is responsive to a variety of stress factors. The expression level of ATF3 is associated with initiation, progression, invasion and metastasis of various cancers, but the mechanism remains unclear. Our group has observed that arsenic upregulated ATF3 in human bronchial epithelial cells (BEAS-2B), and upregulation of ATF3 mediated the expression of CDC25A, GADD45α and Egr-1. This project will establish two in vitro models: high concentration arsenic-mediated cell injury and low dose arsenic-induced BEAS-2B transformation, and use techniques including anti-sense techniques and molecular biology techniques to reveal the effect of ATF3 on arsenic-induced BEAS-2B cell injury, transformation and epithelial-mesenchymal transition (EMT). The ultimate purpose is to understand the inhibitory role of ATF3 in arsenic-induced lung cancer and to provide supporting evidence to identify ATF3 as a target for prevention, treatment and prognosis of arsenic-induced lung cancer.