Estrogen Receptor Mediates the Radiosensitivity of Triple-Negative Breast Cancer Cells.
Estrogen Receptor Mediates the Radiosensitivity of Triple-Negative Breast Cancer Cells.
复制标题
雌激素受体介导三阴性乳腺癌细胞的放射敏感性
DOI：
10.12659/msm.904810
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发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Guo X
中科院分区：
文献类型：
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作者：
Chen X;Ma N;Zhou Z;Wang Z;Hu Q;Luo J;Mei X;Yang Z;Zhang L;Wang X;Feng Y;Yu X;Ma J;Guo X
本研究旨在探讨三阴性乳腺癌（triple-negative breast cancer，TNBC）和腔型乳腺癌细胞放射敏感性的差异，以及雌激素受体（estrogen receptor，ER）表达对TNBC细胞生物学行为的影响。材料/方法采用集落形成试验检测乳腺癌细胞系放射敏感性的差异。采用基因转染技术将ER α基因导入TNBC细胞，比较ER α基因转染TNBC细胞与ER α基因转染TNBC细胞的放射敏感性差异。CCK-8法观察ER α转染后TNBC细胞增殖的变化。免疫荧光法检测细胞核内γ H2AX灶数。流式细胞仪检测细胞周期分布和凋亡的变化。Western blotting检测自噬相关蛋白的变化。结果TNBC细胞系MDA-MB-231（231个细胞）的放射抗性大于ER α阳性的腔型乳腺癌细胞系MCF-7。ER α转染后231细胞的增殖能力和放射抗性均降低。与231细胞相比，ER α转染的231细胞双链断裂和修复延迟增加，照射后G2/M期阻滞和凋亡增加。ER α转染231细胞后，自噬相关蛋白表达减少，提示照射后231 ER阳性细胞自噬活性降低。结论TNBC细胞比腔型乳腺癌细胞对辐射的抵抗力更强。ER α表达可能在乳腺癌细胞放射敏感性调节中起重要作用。
Background This study aimed to evaluate differences in the radiosensitivities of triple-negative breast cancer (TNBC) and luminal-type breast cancer cells and to investigate the effects of estrogen receptor (ER) expression on the biological behaviors of the cells. Material/Methods Colony-forming assays were performed to detect differences in radiosensitivities in breast cancer cell lines. Gene transfection technology was used to introduce the expression of ERα in TNBC cells to compare the difference in radiosensitivity between the TNBC cells and ERα transfected cells. CCK-8 assays were used to observe changes in the proliferation of TNBC cells after ERα transfection. Immunofluorescence was used to detect the number of γH2AX foci in nuclei. Flow cytometry was used to detect changes in cell cycle distribution and apoptosis. Western blotting was used to detect changes in autophagy-associated proteins. Results The radioresistance of the TNBC cell line MDA-MB-231 (231 cells) was greater than that of ERα-positive luminal-type breast cancer cell line MCF-7. Moreover, 231 cell proliferation and radioresistance decreased after ERα transfection. Interestingly, ERα-transfected 231 cells showed increased double-stranded breaks and delayed repair compared with 231 cells, and ERα-transfected 231 cells showed increased G2/M phase arrest and apoptosis after irradiation compared with those in 231 cells. ERα transfection in 231 cells reduced autophagy-related protein expression, suggesting that autophagy activity decreased in 231 ER-positive cells after irradiation. Conclusions TNBC cells were more resistant to radiation than luminal-type breast cancer cells. ERα expression may have major roles in modulating breast cancer cell radiosensitivity.