γ射线诱发的小鼠淋巴细胞白血病中MDM_2的表达研究(英文)  

Expression of MDM_2 in mice lymphocytic leukemia induced by γ-ray irradiation

作　　者：黄越承[1] 蔡建明[1] 韩玲[1] 高福[1] 崔建国[1] 高建国[1] 

机构地区：[1]第二军医大学海军医学系放射医学教研室,上海200433

出　　处：《第二军医大学学报》2004年第6期598-602,共5页Academic Journal of Second Military Medical University

基　　金：ThisworkissupportedbyNationalNaturalScience FoundationofChina(30170282).

摘　　要：目的观察MDM2在γ射线诱发的小鼠淋巴细胞白血病组织细胞中的表达变化,探讨MDM2在辐射致癌中的作用 及可能的分子机制。方法:用γ射线照射BALB/c小鼠诱发白血病发生,建立辐射致癌动物模型;分别应用Western印迹分析 和原位杂交(ISH)技术,从蛋白水平和mRNA水平检测小鼠胸腺和骨髓组织中MDM2的表达情况;运用免疫沉淀技术检测 MDM2蛋白的磷酸化水平;PCR-SSCP及银染技术用于检测基因突变。结果:癌变组和辐射未癌变组胸腺细胞/骨髓细胞 MDM2蛋白表达水平都高于对照组(P<0.05);而癌变组和辐射未癌变组之间MDM2蛋白水平无明显差异。在γ射线照射后 早期辐射组骨髓MDM2蛋白表达水平也明显高于对照组。ISH结果显示:癌变组织中MDM2阳性反应和阳性率均明显高于 对照组。在癌变组组织中发现有MDM2磷酸化比其他组都明显升高(P<0.05)。辐射组和对照组均未检测到基因突变。结论: MDM2可能参与γ射线诱发的小鼠淋巴细胞白血病的发生和发展过程,作用机制可能与过表达及高磷酸化所致活性增强有 关。MDM2的基因突变在辐射致小鼠白血病发生中不起主要作用。Objective:To investigate the role of the MDM 2 in the process of γ-ray irradiation induced carcinogenesis and its molecular mechanisms.Methods:Radiation-induced leukemia animal model was established by γ-ray irradiation.According to the histological and morphological results,mice were divided into3groups:cancerization group,non-cancerization group and control group.Expression of MDM 2 protein and mRNA in thymus and bone marrow was detected with Western blot and in situ hybridization(ISH)respectively.The phosphorylation level of MDM 2 protein was also examined by immunoprecipitation (IP).PCR-SSCP was performed to detect gene mutation.Results:The protein expression in cells of thymus/bone marrow in irradiation groups was significantly higher than that in control(P<0.05).But expression level had no statistic difference be-tween cancerization group and non-cancerization group.The MDM 2 was found hyperphosphorylated in cancerization group compared with the other groups.No gene mutation was found by SSCP/silver-staining assay in the tumor samples.Conclu-sion:MDM 2 may be involved in the development and progression of leukemia induced by γ-ray irradiation.The over-expres-sion,but not gene mutation,may be responsible for malignant transformation induced by irradiation.Phosphorylation is at least partly attributed to activation of MDM 2 . [

关 键 词：Γ射线 诱发 小鼠 淋巴细胞 白血病 MDM2 表达 

分 类 号：R733.7[医药卫生—肿瘤]