p53在调控DNA损伤所致MDA-MB-231细胞死亡中的作用及其机制  

Involvement of p53 in regulation of DNA damage-induced cell death in MDA-MB-231

作　　者：姜朋涛 胡志芳 高兴春 郭娜 张典 姜凤良 JIANG Pengtao;HU Zhifang;GAO Xingchun;GUO Na;ZHANG Dian;JIANG Fengfiang(Department of Immunology,Xi＇an Medical University,Xi＇an 710021,Shaanxi,China)

机构地区：[1]西安医学院基础医学部免疫学教研室,西安710021

出　　处：《癌变．畸变．突变》2018年第5期349-353,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：陕西省自然科学基础研究基金(2017JM8086);西安医学院博士科研启动基金(2017DOC13)

摘　　要：目的:研究p53在调控DNA损伤所致乳腺癌MDA-MB-231细胞死亡中发挥的作用及其相关机制。方法:采用5 J/m^2短波紫外线(UVC)体外照射MDA-MB-231细胞建立DNA损伤模型,通过Western blot检测磷酸化H2AX以鉴定DNA损伤程度,并采用Western blot检测细胞死亡相关蛋白p21、PARP、磷酸化p53和p53,以及核因子NF-90表达的变化。结果:与对照组比较,5 J/m^2 UVC处理细胞0.5 h后即检测到明显的H2AX磷酸化(P<0.05),表明成功建立了DNA损伤模型;同时,p21发生降解并持续保持低表达状态,p53开始发生磷酸化(p-p53增加,P<0.05),处理8 h后观察到PARP的剪切增加(P<0.05),而p53和NF-90蛋白表达未发现明显改变。结论:MDA-MB-231细胞通过p21-PARP途径发生死亡,而磷酸化p53的增加则可以促进细胞存活,从而抑制DNA损伤引起的细胞死亡。OBJECTIVE： To investigate protective effect against cell death in DNA damage-induced breast cancer cell line MDA-MB-231. METHODS： MDA-MB-231 cells were irradiated with 5 J/m^2 UVC and were used to establish our DNA damage cell model. Western blot was used to detect DNA damage marker phospho-H2AX; cell death related proteins： p53, p21, and PARP; and nuclear factor NF-90 which regulates p53 and p21 expression. RESULTS： At 0.5 h after 5 J/m^2 UVC irradiation of MDA-MB-231 cells, phospho-H2AX expression was induced （P〈0.05）, p21 was degraded （P〈0.05）, and phosphor-p53 （p-p53） was induced （P〈0.05）. At 8 hours after irradiation, PARP was cleaved （P〈0.05）. There were not any significant changes on p53 and NF-90. CONCLUSION： From our cell model of DNA damage in MDA-MB-231 cell line, p21-PARP pathway was involved in induction of cell death, but phosphor-p53 was resistant. These imply that phosphor-p53 showed a protective role on this model.

关 键 词：乳腺癌 DNA损伤 细胞死亡 P53 P21 

分 类 号：R737.9[医药卫生—肿瘤]