胃癌细胞中视黄酸受体抑制AP-1活性的不同方式  

Distinct Ways of Retinoic Acid Receptors on Inhibition of AP-1 Activity in Gastric Cancer Cells

作　　者：吴乔[1] 

机构地区：[1]厦门大学生命科学学院

出　　处：《中国生物化学与分子生物学报》2001年第4期430-435,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家杰出青年科学基金 (B类3982 5 5 0 2 );国家自然科学基金 (39880 0 15 )资助&&

摘　　要：研究胃癌细胞中视黄酸受体RARα和RARβ抑制活化蛋白 1(activatorprotein 1,AP 1)活性的不同方式及其与全反式视黄酸 (ATRA)作用的相关性 .瞬时转染RARβ表达载体到MKN 4 5细胞后 ,佛波脂 (TPA)诱导的AP 1活性受到明显抑制 ,且与RARβ浓度正相关 ,与ATRA存在与否无关 ;相反 ,RARα转染细胞后 ,对TPA诱导的AP 1活性的抑制不仅与RARα的浓度相关 ,而且依赖于AT RA .凝胶阻抑测定表明 ,TPA可以显著加强AP 1结合活性 ,当ATRA处理不表达RARβ和低表达RARα的MKN 4 5细胞后 ,AP 1结合活性不受影响 ;然而 ,表达RARα和RARβ的BGC 82 3细胞经AT RA处理后 ,TPA诱导的AP 1结合活性则受到抑制 .另外 ,分析与抗AP 1活性相关的RARβ功能区表明 ,DNA结合区的缺失导致RARβ抑制AP 1活性作用的丧失 ,而配体结合区对于RARβ抑制AP 1活性则是非必需的 .以上结果证实 ,有胃癌细胞中 ,RARβ可能是AP 1活性的抑制因子 ,RARα则可能是ATRA作用的靶向 .尽管它们的作用方式有所不同 ,但最终都可以通过抑制APDistinct ways between RARα (retinoic acid receptor α) and RARβ on inhibition of AP 1(activator protein 1) activity in gastric cancer cells and their relationship with ATRA (all trans retinoic acid) action were investigated.Transient transfection of RARβ expression vector into MKN 45 cells resulted in the significant and RARβ concentration dependent repression of AP 1 activity induced by TPA,regardless of the absence or presence of ATRA.In contrast,inhibition of TPA induced AP 1 activity by RARα required ATRA treatment and was also in an RARα concentration dependent manner.Furthermore,gel retardation assay was carried out and indicated that treatment of gastric cancer cells with TPA strongly enhanced AP 1 binding activity,whereas treatment with ATRA did not affect AP 1 binding in MKN 45 cells,which did not express RARβ but expressed RARα in a very low level.However,when BGC 823 cells,which expressed both RARα and RARβ in a high level,were treated with ATRA,TPA induced AP 1 binding activity was repressed obviously.In addition,the function domains of RARβ,which was responsible for anti AP 1 activity,were analyzed by different RARβ mutants.It was revealed that the deletion of DNA binding domain caused RARβ to be ineffective in the inhibition of AP 1 activity.However,ligand binding domain was not the necessary portion for the inhibition of AP 1 activity.These data strongly suggest that RARβ may be an inhibitor of AP 1 activity and RARα may be a target of ATRA action in gastric cancer cells,they function with ATRA in distinct ways,and then contribute to the growth inhibition of gastric cancer cells through anti AP 1 activity.

关 键 词：视黄酸受体 全反式视黄酸 AP-1活性 胃癌细胞 

分 类 号：R735.2[医药卫生—肿瘤] Q279[医药卫生—临床医学]