p53在调控DNA损伤所致MDAMB-231细胞死亡中的作用及其机制

doi:10.3969/j.issn.1004-616x.2018.05.004

癌变·畸变·突变 ›› 2018, Vol. 30 ›› Issue (5): 349-353.doi: 10.3969/j.issn.1004-616x.2018.05.004

p53在调控DNA损伤所致MDAMB-231细胞死亡中的作用及其机制

姜朋涛, 胡志芳, 高兴春, 郭娜, 张典, 姜凤良

西安医学院基础医学部免疫学教研室, 西安 710021

收稿日期:2018-05-10 修回日期:2018-09-03 出版日期:2018-09-30 发布日期:2018-09-30
通讯作者: 姜凤良,E-mail:fengliangjiang@126.com E-mail:fengliangjiang@126.com
作者简介:姜朋涛,E-mail:jiangpt@xiyi.edu.cn。
基金资助:
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）

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

JIANG Pengtao, HU Zhifang, GAO Xingchun, GUO Na, ZHANG Dian, JIANG Fengliang

Department of Immunology, Xi an Medical University, Xi'an 710021, Shaanxi, China

Received:2018-05-10 Revised:2018-09-03 Online:2018-09-30 Published:2018-09-30

摘要/Abstract

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/m²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Westernblot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/m² 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。

关键词: 乳腺癌, DNA损伤, 细胞死亡, p53, p21

Abstract: OBJECTIVE:To investigate protective effect against cell death in DNA damage-induced breast 2 cancer cell line MDA-MB-231. METHODS:MDA-MB-231 cells were irradiated with 5 J/m² 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. 2 RESULTS:At 0.5 h after 5 J/m² 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.

Key words: breast cancer, DNA damage, cell death, p53, p21

中图分类号:

R737.9

姜朋涛, 胡志芳, 高兴春, 郭娜, 张典, 姜凤良. p53在调控DNA损伤所致MDAMB-231细胞死亡中的作用及其机制[J]. 癌变·畸变·突变, 2018, 30(5): 349-353.

JIANG Pengtao, HU Zhifang, GAO Xingchun, GUO Na, ZHANG Dian, JIANG Fengliang. Involvement of p53 in regulation of DNA damage-induced cell death in MDA-MB-231[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(5): 349-353.

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p53在调控DNA损伤所致MDAMB-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

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