期刊
CANCER BIOLOGY & THERAPY
卷 11, 期 12, 页码 1028-1035出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.11.12.15699
关键词
cancer stem cells; homologous recombination; ionizing radiation; cell cycle; breast cancer; non-homologous end joining; cancer stem-like cells
类别
资金
- MRC [G0700730]
- CRUK
- Cancer Research UK [6947] Funding Source: researchfish
- Medical Research Council [G0700730] Funding Source: researchfish
- MRC [G0700730] Funding Source: UKRI
The concept of cancer stem cells is generally accepted in different malignancies. We have previously shown that the MDA-MB231 breast cancer cells were more radiation resistant when sorted for the two stem cell markers CD24 and ESA. In this study, we examined a possible mechanism that might underlie this phenotype by looking at cell cycle profile and the effect this has on DNA repair pathways. The cell cycle profile showed that there were more CD24 ESA(+) sorted MDA-MB231 cells in the S- and G(2)-phases compared with the unsorted cells, 60 and 38% respectively. Cyclin D and E protein levels supported the cell cycle profile and highlighted the possible involvement of homologous recombination (HR) repair in the radioresistant phenotype. To further support this, CD24 ESA(+) sorted MDA-MB231 cells demonstrated statistically significant more RAD51 and less gamma H2AX foci 2 h post 4 Gy ionizing radiation, compared with the unsorted population Inhibition of the HR pathway effectively sterilized the CD24-ESA(+) sorted MDA-MB231 cells but had no effect on the unsorted cells or MDA468 control breast cancer cell line. Although the changes we saw were specific to MDA-MB231, these results merit further investigation and can be crucial in identifying a mechanism responsible for cancer stem cells treatment resistance in primary tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据