EGF_PI3K_Akt信号通路对TEIF蛋白功能的调节作用及意义.docVIP

 TEIF associated centrosomal activity is regulated by EGF/PI3K/Akt signaling# 5 10 15 20 25 30 35 40 ZHAO Jing, CHI Yingkai, LIU Haijing, ZOU Yongxin, CUI Suping, JIANG Ping, WANG Huali, ZHANG Hong, MAO Jingzhuo, HOU Lin, ZHANG Bo ** (Department of Pathology, Basic School of Medical Science, Health Science Center of Peking University, Beijing 100191 China) Abstract: Centrosome amplification, a characteristic of cancer cells, has been believed a driving force for genetic instability in the development of cancer and received extensively exploration in recent years. In our previous work, we have demonstrated that TEIF（transcriptional elements-interacting factor） distributes at the centrosome and regulates its status in physiological condition, DNA damage response or carcinogenesis. Here, we further expand our knowledge of TEIF to the downstream effector of EGF/PI3K/Akt signaling. The addition of EGF or transfection of active Akt stimulated TEIF expression, resulting in an increase of centrosome splitting and amplification, while the inhibitors of either PI3K or Akt attenuated the changes in TEIF and its associated centrosome status. A consensus motif for Akt phosphorylation (RHRVLT) was revealed in TEIF domain of localizing at the centrosome and identified as the site for phosphorylation of TEIF both in vitro and in vivo experiments, indicating TEIF as a direct substrate to Akt1. Furthermore, in a collection of aggressive breast cancers a positive correlation between the expression of TEIF and centrosome amplification was clarified and also closely concerned to the over-expression of CerbB2 (a member of EGFR family) and the level of phosphorylated Akt (pAkt) in cancer tissues. These findings not only could link EGF/PI3K/Akt oncogenic signaling with centrosome amplification, but also could provide more choices in the development of specific inhibitors for anti-cancer therapeutic agents targeting to EGF/PI3K/Akt signaling. Key words: Centrosome amplification; EGF;