肠型胃癌的发生经过慢性萎缩性胃炎-肠化生-异形增生至胃癌，其中伴有明显的细胞分化障碍，前期研究发现胃癌组织中雄激素受体（AR）高表达，且与MAGE-A11具有共表达现象，AR是一种核受体，为配体依赖性转录因子。本项目拟在前期研究的基础上证明如下科学假说，慢性炎症微环境上调AR和MAGE-A11表达，AR和MAGE-A11结合入核后招募共因子（CBP/p300、FOXA1、GATA2），在CBP/p300介导下组蛋白乙酰化，启动下游转录因子CDX1和Snail表达，从而导致胃上皮细胞分化障碍，为胃癌的发生创造必要的条件，揭示AR在促进胃癌细胞分化障碍、细胞增殖、EMT等的分子机制；为将基于AR的靶向治疗策略应用于胃癌个体化治疗奠定理论与实验基础。

The intestinal gastric cancer develops from chronic atrophy gastritis, intestinal metaplasia, dysplasia,to carcinoma. This carcinogenesis sequence accompany with cell dys-differentiation. Our previous work found that androgen receptor (AR) expression was upregulated and co-expressed with MAGE-A11 in GC tissues. As a nuclear receptor, AR is a ligand-dependent transcription factor. Based on the previous found, the aims of present project are to illustrate scientific hypothesis as follows. AR and MAGE-A11 were upregulated in chronic inflammatory microenvironment. Then AR combines with MAGE-A11 and transfers into nucleus then recruiting co-factors (such as, CBP/p300, FOXA1, GATA2), in turn induce differentiation disorder of gastric epithelium by activating downstream transcription factors CDX1 and Snail, which crate a necessary condition for gastric cancer development. The present project contributes to further understand biological function of AR in carcinogenesis of GC ,demonstrate the mechanisms of that activating AR transfers into nucleus and recruits co-activator and co-repressor through which activating critical downstream genes in inflammatory microenvironment, and then illustrate the mechanisms of AR on promoting cell differentiation disorder, proliferation, and EMT. The study will establish a theoretical and experimental foundation for GC individualized treatment based on therapeutic strategy targeting on AR.