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Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells

文献类型：期刊论文

作者Yang, Pengfei1,4,5; Feng, Xiu1,4,5; Li, Jin2,4,5; Zhang, Tianyi1,4,5; Sheng, Chengyan2,4,5; Zhang, Liying3; Hua, Junrui1,4,5; Wei, Wenjun1,4,5; Ding, Nan1,4,5; He, Jinpeng1,4,5
刊名CELL DEATH & DISEASE
出版日期2021-10-29
卷号12期号:11页码:10
ISSN号2041-4889
DOI10.1038/s41419-021-04328-w
通讯作者Wang, Jufang(jufangwang@impcas.ac.cn) ; Zhou, Heng(hengzhou@impcas.ac.cn)
英文摘要Breast cancer is a major threat to women's health and estrogen receptor-positive (ER+) breast cancer exhibits the highest incidence among these cancers. As the primary estrogen, estradiol strongly promotes cellular proliferation and radiotherapy, as a standard treatment, exerts an excellent therapeutic effect on ER+ breast cancer. Therefore, we herein wished to explore the mechanism(s) underlying the inhibitory effects of radiation on the proliferation of ER+ breast cancer cells. We used the ER+ breast cancer cell lines MCF7 and T47D, and their complementary tamoxifen-resistant cell lines in our study. The aforementioned cells were irradiated at different doses of X-rays with or without exogenous estradiol. CCK8 and clone-formation assays were used to detect cellular proliferation, enzyme-linked immunosorbent assay (ELISA) to determine estradiol secretion, western immunoblotting analysis and quantitative real-time PCR to evaluate the expression of proteins, and immunofluorescence to track endoplasmic reticulum stress-related processes. Finally, BALB/C tumor-bearing nude mice were irradiated with X-rays to explore the protein expression in tumors using immunohistochemistry. We found that ionizing radiation significantly reduced the phosphorylation of estrogen receptors and the secretion of estradiol by ER+ breast cancer cells. CYP19A (aromatase) is an enzyme located in the endoplasmic reticulum, which plays a critical role in estradiol synthesis (aromatization), and we further demonstrated that ionizing radiation could induce endoplasmic reticulum stress with or without exogenous estradiol supplementation, and that it downregulated the expression of CYP19A through ER-phagy. In addition, ionizing radiation also promoted lysosomal degradation of CYP19A, reduced estradiol synthesis, and inhibited the proliferation of tamoxifen-resistant ER+ breast cancer cells. We concluded that ionizing radiation downregulated the expression of CYP19A and reduced estradiol synthesis by inducing endoplasmic reticulum stress in ER+ breast cancer cells, thereby ultimately inhibiting cellular proliferation.
WOS关键词ER STRESS ; RESISTANCE ; ACTIVATION ; AUTOPHAGY ; ALPHA
资助项目National Nature Science Foundation of China[11905264] ; Science and Technology Research Project of Gansu Province[17JR5RA307] ; Science and Technology Research Project of Gansu Province[145RTSA012]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000712879100005
出版者SPRINGERNATURE
资助机构National Nature Science Foundation of China ; Science and Technology Research Project of Gansu Province
源URL[http://119.78.100.186/handle/113462/138319]  
专题中国科学院近代物理研究所
通讯作者Wang, Jufang; Zhou, Heng
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Lanzhou Univ, Sch Nucl Sci & Technol, Lanzhou, Peoples R China
3.Gansu Univ Chinese Med, Lanzhou, Peoples R China
4.Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou, Peoples R China
5.Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Pengfei,Feng, Xiu,Li, Jin,et al. Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells[J]. CELL DEATH & DISEASE,2021,12(11):10.
APA Yang, Pengfei.,Feng, Xiu.,Li, Jin.,Zhang, Tianyi.,Sheng, Chengyan.,...&Zhou, Heng.(2021).Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells.CELL DEATH & DISEASE,12(11),10.
MLA Yang, Pengfei,et al."Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells".CELL DEATH & DISEASE 12.11(2021):10.

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来源：近代物理研究所

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