文献类型：期刊文献

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

作者：Yang, Pengfei[1,2,3];Feng, Xiu[1,2,3];Li, Jin[1,2,4];Zhang, Tianyi[1,2,3];Sheng, Chengyan[1,2,4];Zhang, Liying[5];Hua, Junrui[1,2,3];Wei, Wenjun[1,2,3];Ding, Nan[1,2,3];He, Jinpeng[1,2,3];Zhang, Yanan[1,2,3];Wang, Jufang[1,2,3];Zhou, Heng[1,2,3]

第一作者：Yang, Pengfei

通信作者：Wang, JF[1];Zhou, H[1];Wang, JF[2];Zhou, H[2];Wang, JF[3];Zhou, H[3]

机构：[1]Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou, Peoples R China;[2]Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Peoples R China;[3]Univ Chinese Acad Sci, Beijing, Peoples R China;[4]Lanzhou Univ, Sch Nucl Sci & Technol, Lanzhou, Peoples R China;[5]Gansu Univ Chinese Med, Lanzhou, Peoples R China

第一机构：Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou, Peoples R China;[2]corresponding author), Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Peoples R China;[3]corresponding author), Univ Chinese Acad Sci, Beijing, Peoples R China.

年份：2021

卷号：12

期号：11

外文期刊名：CELL DEATH & DISEASE

收录：;Scopus(收录号：2-s2.0-85118464740);WOS:【SCI-EXPANDED(收录号:WOS:000712879100005)】；

基金：This work was supported by the National Nature Science Foundation of China (number 11905264), the Science and Technology Research Project of Gansu Province (number 17JR5RA307 and number 145RTSA012).

语种：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.