ATF1在肺腺癌发生发展中的作用及机制研究

肺腺癌是最常见的恶性肿瘤之一，其发病率和死亡率较高且预后较差，严重危害着人类的健康及生命。肺腺癌的发生发展是一个多因素、多步骤的过程，其发病机理非常复杂，到目前为止其确切发病机理尚未完全清楚。我们的初步研究结果发现，转录激活因子1（ATF1）在人肺腺癌组织中高表达，且ATF1过表达可促进肺腺癌细胞内锌指转录因子143（ZNF143）的表达。鉴于ZNF143在肿瘤组织中高表达并与肿瘤的发生发展密切相关，提示ATF1可能通过调控ZNF143的表达而促进肺腺癌的发生发展。本课题将首先明确ATF1和ZNF143蛋白是否在人肺腺癌组织和肺腺癌细胞系中高表达；然后用基因定点突变和染色质免疫共沉淀等方法确定ATF1与ZNF143基因启动子区域结合；并最终确定ATF1通过调控ZNF143的基因转录而促进肺腺癌的发生。本课题的研究可为肺腺癌的发病机理提供新的理论基础和实验依据。

Lung adenocarcinoma is one of the most common cancers and a main cause of cancer-related death worldwide. In these settings, lung adenocarcinoma patients are usually faced with a very poor prognosis. The occurrence and development of lung adenocarcinoma are affected by multi-factors and multi-steps, the precise mechanism is yet to be defined. Our preliminary results found that activating transcription factor 1 (ATF1) was highly expressed in human lung adenocarcinoma, we also found that overexpression of ATF1 could up-regulate the mRNA level of Zinc finger protein 143 (ZNF143) in lung adenocarcinoma cell. Inasmuch as ZNF143 is highly expressed in cancer and involved in tumor progression. These results indicated that ATF1 might promote lung adenocarcinoma progression via regulating ZNF143 expression. Therefore, we will investigate these hypotheses: (1) whether the protein levels of ATF1 and ZNF143 were significantly higher in lung adenocarcinoma specimens and lung adenocarcinoma cell lines, (2) Site-directed mutagenesis and chromatin immunoprecipitation assay will be used to assess binding of ATF1 to ZNF143 gene promoter in these cells and (3) whether ATF1 promotes lung adenocarcinoma progression via regulating transcription of ZNF143 gene. The present study will provide a novel insight into the mechanism of lung adenocarcinoma.