γ射线诱发小鼠皮肤汗腺癌中p53、MDM2基因的表达

Expression of p53、MDM2 in a mice hydradecarcinoma model induced by γ-ray irradiation

目的 观察p5 3、MDM2在γ射线诱发的小鼠皮肤汗腺癌组织中的表达 ,探讨p5 3、MDM2在辐射诱发皮肤汗腺癌中的作用。方法 用γ射线照射BALB/c小鼠诱发皮肤汗腺癌 ,建立辐射致癌动物模型 ;应用Westernblot技术检测小鼠汗腺癌组织、癌旁组织及正常对照组织中的MDM2蛋白表达情况 ;运用免疫沉淀技术 (IP)检测MDM2蛋白的磷酸化水平 ;PCR SSCP及银染技术用于检测p5 3基因突变。结果 癌变组织的MDM2蛋白表达水平高于正常组织和癌旁组织 ,而且MDM2磷酸化水平明显升高 (P <0 0 5 )。SSCP检测到的p5 3基因异常比野生型增多或缺失条带。结论 p5 3/MDM2途径参与γ射线诱发的小鼠皮肤汗腺癌的发生和发展过程 ,作用机制可能与MDM2过表达及高磷酸化和p5 3基因突变有关。

Objective To investigate the role of the p53,MDM2 in carcinogenesis of mice hydradecarcinoma induced by γ-rays. Methods A radiation-induced mice hydradecarcinoma model was established by γ-ray irradiation. Expression of MDM2 protein in hydradecarcinoma tissue,paracancerous tissue and normal control tissue was detected with Western blot. Immunoprecipitation (IP) was conducted to examine the phosphorylation level of MDM2 protein. PCR-SSCP was performed to detect p53 gene mutation. Results Compared with the normal control tissue,the MDM2 protein expression and its phosphorylation level were significantly higher in hydradecarcinoma tissue. SSCP showed there were p53 gene mutations in hydradecarcinoma samples. Conclusion p53/MDM2 pathway may be involved in the development and progression of hydradecarcinoma induced by γ-ray irradiation. The over-expression of MDM2 and hyperphosphorylation may be responsible for malignant transformation induced by irradiation by a possible mechanism of p53 inactivation. The gene mutation of p53 further supported the hypothesis that p53/MDM2 pathway played a central role in carcinogenesis of γ-ray induced hydradecarcinoma.;