生物学杂志

• 研究报告 • 上一篇    下一篇

转录因子FOXA1在乳腺癌分子分型中的功能研究

  

  1. 1. 江南大学 粮食发酵工艺与技术国家工程实验室; 2.江南大学 生物工程学院,无锡 214122
  • 出版日期:2017-02-18 发布日期:2017-02-18
  • 通讯作者: 戴晓峰,副教授,主要从事乳腺癌分型及靶向药物研究,E-mail:xiaofeng.dai@me.com
  • 作者简介:白仲虎,教授,主要从事生物医药研究与开发,E-mail:baizhonghu@jiangnan.edu.cn
  • 基金资助:
    国家自然科学基金项目(31471251)

Research on function of transcription factor FOXA1 in breast cancer subtyping

  1. 1. National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University;2. School of Biotechnology, Jiangnan University, Wuxi 214122, China
  • Online:2017-02-18 Published:2017-02-18

摘要: 乳腺癌作为高度异源性的疾病,其准确的分子分型对于乳腺癌预后判断和制定合理的治疗方案都具有十分重要的临床意义。通过前期生物信息学分析认为foxa1在乳腺癌中具有重要的分子分型作用,利用免疫印迹法及实时定量PCR方法在涵盖4个乳腺癌亚型的10个乳腺癌细胞株中检测FOXA1的mRNA及蛋白表达水平情况,探索其与乳腺癌分子亚型之间关联,以及在肿瘤发生、发展及预后中的意义。结果显示,FOXA1的mRNA和蛋白表达量在乳腺癌Luminal A型和Luminal B型中显著高于其在Her2过表达型和三阴性型乳腺癌细胞株中的表达量。通过对其他促进细胞生长的重要基因表达量的关联分析以及基因沉默实验,发现FOXA1是介于GATA3和ER的关键调控元素,其高表达能够抑制细胞增殖。研究提出foxa1可以作为辅助分子对乳腺癌进行精准分型,验证了前期的生物信息学结论,推动了乳腺癌精准医学的发展。

关键词: 乳腺癌, FOXA1, 分子分型, 转录因子

Abstract: Breast cancer is a highly heterogeneous disease. Its accurate molecular subtyping helps us to improve the precision of breast cancer prognosis and the corresponding therapeutic decision making. By comparing the transcriptional and translational expression of foxa1 among breast cancer cell lines, the previous hypothesis that FOXA1 is a critical factor discriminating breast cancer subtypes was validated. In addition, by silencing foxa1 and observing the subsequent proliferation and apoptosis, the roles of FOXA1 played in breast cancer occurrence, development and prognosis were explored. Analyzing the expression of foxa1 in 10 cell lines covering four subtypes by Western Blot and real-time quantitative PCR, the expression of foxa1 in Luminal A and Luminal B breast cancers was significantly higher than that in Her2 positive and Triple negative subtypes. By analyzing the expression of other genes that promote cell growth, the result showed that FOXA1 was a key regulatory factor between GATA3 and ER, which inhibited cell proliferation.

Key words: breast cancer, FOXA1, molecular subtypes, transcription factor