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

doi:10.1038/s41419-021-04328-w

	Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells
	Yang, Pengfei 1,4,5; Feng, Xiu 1,4,5; Li, Jin 2,4,5; Zhang, Tianyi 1,4,5; Sheng, Chengyan 2,4,5; Zhang, Liying 3; Hua, Junrui 1,4,5; Wei, Wenjun 1,4,5; Ding, Nan 1,4,5; He, Jinpeng 1,4,5
刊名	CELL DEATH & DISEASE
	2021-10-29
卷号	12 期号:11 页码:10
ISSN号	2041-4889
DOI	10.1038/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.
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关键词	ER STRESS ; RESISTANCE ; ACTIVATION ; AUTOPHAGY ; ALPHA
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000712879100005
资助机构	National Nature Science Foundation of China ; Science and Technology Research Project of Gansu Province
内容类型	期刊论文
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.