乳腺癌TGF-β信号通路相关转录因子研究进展

Research of transcription factors involved in TGF-β signaling pathway in breast cancer

目的总结与转化生长因子β(transforming growth factor-β,TGF-β)信号通路相关的转录因子在乳腺癌发生发展过程中的作用,分析它们与TGF-β信号通路之间的网络调控机制。方法应用PubMed及CNKI期刊全文数据库检索系统,以"乳腺癌、转录因子和TGF-β"等为关键词,检索2011-01-01-2015-12-31的相关文献。纳入标准:(1)乳腺癌侵袭转移;(2)转录因子与TGF-β信号通路存在联系。剔除标准:(1)未阐明转录因子与TGF-β信号通路作用的具体机制;(2)实验设计不严谨。符合纳入标准的英文文献146篇,中文文献35篇,根据剔除标准剔除英文文献50篇,中文文献34篇,最后纳入分析文献88篇。结果 TGF-β信号通路是一条极为重要的细胞内信号转导途径,能调控细胞增殖、分化、迁移、粘附及凋亡等生理活动。在乳腺癌中,TGF-β信号通路起着双重作用,即在肿瘤发生的早期阶段,TGF-β信号通路起着一种预防性或肿瘤抑制的作用,但随着肿瘤的发展,TGF-β能够通过影响肿瘤微环境、增强侵袭性及抑制免疫细胞功能来促进肿瘤细胞的转移。多个转录因子c-Myc、p53、C/EBPβ、14-3-3ζ、Blimp-1、Oct-4和Nanog、Foxq1、TBX3、FOXM1、GATA3、HOXB9、Six1、Pokemon、Snail、Slug和SOX4已证实与TGF-β信号通路发生相互作用,共同参与调控乳腺癌发生发展过程。结论乳腺癌发生过程中转录因子与TGF-β信号通路形成复杂的调控网络,对乳腺癌的进程起着双向调节作用。

OBJECTIVE To Summarize the research situation of transcription factors involved in TGF-β signaling pathway in breast cancer progression, and analyze the cross talk between TGF -β signaling pathway and transcription fac tors. METHODS To retrieve the articles from 2011 to 2015 by PubMed and CNKI full test database retrieval system with ＂breast cancer, transcription factors,TGF-β＂ as key words and get 914 English articles and 68 Chinese ones. Selec- tion standard： （1）Invasion and metastasis of breast cancer. （2）The interaction between transcription factors and TGF-β signaling pathway. Excluson standard： （1）transcription factors without function cerification on TGF-β signaling path way. （2）Experimental design is not rigorous. According to the selection standard, 146 English articles and 35 Chinese ones meet the requirement. According to the Excluson standard, 50 English articles and 34 Chinese ones were excluded, and 88 articles were selected at last. RESULTS TGF-β signaling pathway is an extremely important cell signal transduc tion pathway that can regulate cell proliferation, differentiation, migration, adhesion and apoptosis. In breast cancer, TGFβ signaling has been reported to elicit a preventative or tumor suppressive effect during the earlier stages of tumorigenesis, in the later stage of tumor development, TGF-β signaling can promote invasion and inhibit the immune cells＇ function to facilitate the metastasis of tumor cells via affecting the tumor microenvironment. The transcription factors： c Myc, p53, C/EBPβ, 14 3-3ξ, Blimp 1, Oct-4 and Nanog, Foxql, TBX3, FOXM1, GATA3, HOXB9, Six3, Poke mon, Snail,Slug and SOX4 have been shown to interact with TGF-βsignaling pathway, and participate in the regulation of breast cancer progression. CONCLUSION The transcription factors present a complicated net work with TGF -β signaling which exerts dual roles in the progression of breast cancer.