| Yang Tianpeng,Zhang Shinan,Ji Huilin,Zhu Linhui,Zhang Yujie,Huang Jin,Wen Yingren,Ma Shumei,Liu Xiaodong.Mechanisms on radiation resistance induced by an estrogen receptor in breast cancer cells[J].Chinese Journal of Radiological Medicine and Protection,2024,44(2):88-95 |
| Mechanisms on radiation resistance induced by an estrogen receptor in breast cancer cells |
| Received:November 13, 2023 |
| DOI：10.3760/cma.j.cn112271-20231113-00169 |
| KeyWords:Estrogen Receptor 1 Autophagy Ionizing radiation Breast cancer cell |
| FundProject:国家自然科学基金(81972969);浙江省自然科学基金(LY23H220001) |
| Author Name | Affiliation | E-mail | | Yang Tianpeng | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | | | Zhang Shinan | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | | | Ji Huilin | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China
Southern Zhejiang Institute of Radiological Medicine and Nuclear Technology Application, Wenzhou Medical University, Wenzhou 325035, China | | | Zhu Linhui | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China
Southern Zhejiang Institute of Radiological Medicine and Nuclear Technology Application, Wenzhou Medical University, Wenzhou 325035, China | | | Zhang Yujie | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | | | Huang Jin | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | | | Wen Yingren | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | | | Ma Shumei | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China
Southern Zhejiang Institute of Radiological Medicine and Nuclear Technology Application, Wenzhou Medical University, Wenzhou 325035, China | | | Liu Xiaodong | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China
Southern Zhejiang Institute of Radiological Medicine and Nuclear Technology Application, Wenzhou Medical University, Wenzhou 325035, China | liuxd2014@126.com |
|
| Hits: 569 |
| Download times: 168 |
| Abstract:: |
| Objective To explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining. Results Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death (t = 3.49, 3.13,P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death (t = 4.16, 7.48,P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells (t = 8.49,P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death (t = 4.19, 6.39,P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown (t = 1.70, 4.65,P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death (t = 18.70,P < 0.05). Furthermore, these processes were promoted by ionizing radiation (t = 16.82,P < 0.05).Conclusions The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells. |
| HTML View Full Text View/Add Comment Download reader |
| Close |
|
|
|
