14-3-3σ负调控Akt抑制Rat1-Akt细胞成瘤性  

14-3-3σ negatively regulates Akt and inhibits Rat1-Akt cell xenografts

作　　者：夏洪平[1] 杨惠玲[1] 夏云飞[2] 黄文林[2] LEE Mong-hong 苏勇[2] 

机构地区：[1]中山大学病理生理学教研室,广东广州510080 [2]中山大学肿瘤防治中心,广东广州510060 [3]美国德州大学M.D.Anderson癌症中心

出　　处：《中国病理生理杂志》2006年第12期2368-2371,共4页Chinese Journal of Pathophysiology

基　　金：广东省重大科技专项基金资助项目(No.2004A30801006);广东省国际合作科技计划项目(No.2004B50301003);广州市国际合作项目(No.4205001)

摘　　要：目的:研究腺病毒介导14-3-3.σ(Ad-14-3-.3σ)对Akt过表达Rat1-Akt细胞成瘤性的作用,并探讨其作用是否通过负调控Akt而实现。方法:通过半体内和体内实验观察Ad-14-3-.3σ转染对Rat1-Akt细胞在裸鼠中成瘤性的影响;采用W estern b lotting方法检测转染14-3-.3σ基因后肿瘤组织内14-3-.3σ蛋白及其对Akt蛋白、Akt磷酸化活性和Akt磷酸化底物水平的影响。结果:无论体外用Ad-14-3-3σ处理Rat1-Akt细胞,还是体内经瘤内注射Ad-14-3-3σ,均可见14-3-3.σ可使荷瘤鼠肿瘤体积显著缩小(P<0.05),出现肿瘤的时间推迟,其中以长时间不间断给药疗效最好;转染14-3-.3σ基因治疗组的肿瘤组织中Akt蛋白、Akt-Thr308位点磷酸化活性及Akt磷酸化底物水平低于转染Ad-β-gal或PBS处理的对照组。结论:14-3-3σ可抑制Rat1-Akt细胞在裸鼠中的成瘤性,14-3-3σ通过负性调控Akt蛋白水平和磷酸化活性而抑瘤。AIM ： The present study was designed to investigate the effect of adenovirus - mediated 14 - 3 - 3σ on Ratl- Akt cell xenografts and to explore whether the effect was mediated through negative regulation of Akt. METHODS ： The effect of Ad - 14 - 3 - 3σ on Ratl- Akt cells xenografts was observed in nude mice ex vivo and in vivo. Western blotting was used to detect 14 - 3 - 3or protein,phospho - Akt （ Thr 308） , phospho - Akt （ Ser 473）, and phospho - （ Ser/ Thr） Akt substrate in tumor tissue after transfeetion of 14 -3 -3σ gene. RESULTS： The tumor volume was dramatically decreased and its emergence was delayed, regardless of using Ad - 14 -3 -3σ -treated Ratl -Akt cells （ex vivo） or injeeted Ad - 14 - 3 - 3σ in vivo, of which the effect of the continuously injected group was the best. Levels of Akt protein, phosphorylated Akt and phosphorylated Akt substrates in tumors obtained from Ad - 14 - 3 - 3σ - treated mice were markedly less than those in PBS or Ad - β - gal - treated mice, CONCLUSION： 14 - 3 - 3σ suppressed Akt overexpession in cells of Ratl - Akt xenografts by negatively regulating Akt.

关 键 词：基因 14—3—3σ 蛋白激酶B Rat1—Akt细胞 小鼠 裸 

分 类 号：R735.905.3[医药卫生—肿瘤]