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血清和糖皮质激素诱导激酶3表达水平对ER+乳腺癌细胞增殖与凋亡的影响
Serum- and glucocorticoid-regulated kinase 3 promotes proliferation and inhibits apoptosis of ER+ breast cancer cells
- 第三军医大学学报 2021年43卷第22期 页码：2414-2422
- 作者机构：
400016 重庆，重庆医科大学药学院：药理学系，生物化学与分子药理学重庆高校市级重点实验室，药物代谢研究重庆市重点实验室
- 作者简介：
[ 周维英，E-mail：wyzhou0118@163.com ZHOU Weiying, E-mail: wyzhou0118@163.com
- 基金信息：重庆市高校创新研究群体项目(CXQT20012);2018年重庆市研究生导师团队建设项目(dstd201807);重庆市教育委员会科学技术研究项目(KJQN201800431)
DOI：10.16016/j.1000-5404.202105155
中图分类号： R394.3;R730.23;R737.9收稿：2021-05-27，
修回：2021-07-11，
纸质出版：2021-11-30
- 稿件说明：
移动端阅览
刘旭, 李小丽, 周端方, 等. 血清和糖皮质激素诱导激酶3表达水平对ER+乳腺癌细胞增殖与凋亡的影响[J]. 第三军医大学学报, 2021,43(22):2414-2422.
Xu LIU, Xiaoli LI, Duanfang ZHOU, et al. Serum- and glucocorticoid-regulated kinase 3 promotes proliferation and inhibits apoptosis of ER+ breast cancer cells[J]. Journal of Third Military Medical University, 2021, 43(22): 2414-2422.
刘旭, 李小丽, 周端方, 等. 血清和糖皮质激素诱导激酶3表达水平对ER+乳腺癌细胞增殖与凋亡的影响[J]. 第三军医大学学报, 2021,43(22):2414-2422. DOI： 10.16016/j.1000-5404.202105155.
Xu LIU, Xiaoli LI, Duanfang ZHOU, et al. Serum- and glucocorticoid-regulated kinase 3 promotes proliferation and inhibits apoptosis of ER+ breast cancer cells[J]. Journal of Third Military Medical University, 2021, 43(22): 2414-2422. DOI： 10.16016/j.1000-5404.202105155.
摘要
目的
2
探讨血清和糖皮质激素诱导激酶3（serum- and glucocorticoid-regulated kinase 3，SGK3）对ER
+
乳腺癌细胞系MCF-7细胞及T47D细胞增殖和凋亡的影响。
方法
2
利用基因表达谱交互分析（gene expression profile interactive analysis，GEPIA）生物信息学工具，分析癌症公共数据库癌症基因组图谱计划（the cancer genome atlas program
TCGA）中乳腺癌组织（breast cancer tissue，BRCA）及对照样本中SGK3蛋白的表达水平，基于TCGA数据库中的BRCA患者样本进行生存分析；选取SGK3可诱导表达乳腺癌细胞系MCF-7-Tet-On-SGK3及T47D-Tet-On-SGK3为研究对象，在诱导SGK3过表达后，用MTT法检测过表达SGK3对细胞增殖的影响；流式细胞仪及Annexin V-FITC凋亡检测试剂盒检测过表达SGK3对细胞凋亡的影响；免疫印迹方法（Western blot）检测凋亡相关蛋白分子的变化。利用SGK3特异性小干扰RNA（small interference RNA，siRNA）敲低SGK3后，MTT法检测敲低SGK3对细胞增殖的影响。流式细胞术检测细胞凋亡情况，Western blot实验检测凋亡相关蛋白分子变化。
结果
2
TCGA数据库共有1 084例BRCA样本及492例乳腺对照样本，与对照组乳腺组织相比，SGK3在BRCA中显著高表达。GEPIA的生存曲线分析表明，SGK3高表达患者的总生存期(overall survival，OS)及无病生存期(disease free survival，DFS)较低表达患者缩短。在MCF-7-Tet-On-SGK3和T47D-Tet-On-SGK3细胞中，诱导SGK3过表达能够促进细胞增殖和减少细胞凋亡水平（
P
<
0.05）。在分子水平，过表达SGK3能够下调凋亡蛋白Bax和Cleaved-PARP表达，上调抗凋亡蛋白Bcl-2水平（
P
<
0.05）。在MCF-7和T47D细胞敲低SGK3能够抑制细胞增殖活力和增加细胞凋亡（
P
<
0.05）。在分子水平，敲低SGK3能够增加Bax蛋白水平，降低Bcl-2表达和上调Cleaved-PARP水平（
P
<
0.05）。
结论
2
在ER
+
乳腺癌细胞中，SGK3促进细胞增殖、减少细胞凋亡，其高表达可能与乳腺癌患者预后不良有关。
Abstract
Objective
2
To investigate the effects of serum- and glucocorticoid-regulated kinase 3 (SGK3) on the proliferation and apoptosis of ER positive breast cancer cell lines MCF-7 and T47D.
Methods
2
Gene expression profile interactive analysis (GEPIA) was used to analyze SGK3 expression levels in BRCA (breast cancer tissue) and normal tissue in the cancer public database
the Cancer Genome Atlas (TCGA) database
and survival analysis was performed based on SGK3 levels in the BRCA patients in the TCGA database. After inducement of SGK3 overexpression in SGK3-inducible breast cancer cell lines MCF-7-Tet-On-SGK3 and T47D-Tet-On-SGK3
MTT assay was used to detect the effect of SGK3 overexpression on cell proliferation. Flow cytometry and Annexin V-FITC apoptosis detection kit were employed to detect the effect of SGK3 overexpression on cell apoptosis. Western blotting was applied to measure the changes of apoptosis-related protein molecules. After SGK3 was knocked down with SGK3 specific small interference RNA
MTT assay was adopted to detect the effect of SGK3 knockdown on the proliferation of MCF-7 cells
flow cytometry for cell apoptosis
and Western blotting for the molecular changes of apoptosis-related proteins.
Results
2
The TCGA database had a total of 1 084 BRCA samples and 492 breast control samples. Compared with the control breast tissue
the expression of SGK3 was significantly higher in BRCA. The GEPIA survival curve analysis showed that the expression level of SGK3 was negatively correlated with the overall survival (OS) and disease-free survival (DFS) of BRCA patients. In MCF-7-Tet-On-SGK3 and T47D-Tet-On-SGK3 cells
inducing SGK3 expression promoted cell proliferation and reduced the apoptosis. At molecular level
SGK3 overexpression down-regulated the expression of apoptotic proteins Bax and cleaved-PARP
and up-regulated the level of anti-apoptotic protein Bcl-2. SGK3 knockdown in MCF-7 and T47D cells inhibited cell proliferation and increased cell apoptosis. At the molecular level
knocking SGK3 down increased Bax protein level
reduced Bcl-2 level and up-regulated cleaved-PARP.
Conclusion
2
In ER
+
breast cancer
cells
SGK3 promotes cell proliferation and reduces apoptosis. Its high expression may be associated with poor prognosis in breast cancer patients.
关键词
Keywords
references
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