Role of nuclear receptor NR4A2 in gastrointestinal inflammation and cancers

作     者：Yi-Fang Han Guang-Wen Cao 

作者机构：Department of EpidemiologySecond Military Medical University 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2012年第18卷第47期

页      面：6865-6873页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by National Natural Science Foundation of China  No.81025015 30921006 91129301 

主　　题：NR4A2 Inflammation Immune cells Signaling pathway Gastrointestinal carcinoma 

摘      要：NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor *** was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson s ***,NR4A2 has been found to play a critical role in some inflammatory diseases and ***4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune ***4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg ***4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological *** density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease ***4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC *** cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and ***4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor *** of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo *** together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.