STAT1 promotes radioresistance of CD44(+)/CD24(-/low) cells in breast cancer.

Abstract

Breast cancer-initiating cells are a relatively radioresistant subpopulation of breast cancer cells. However, the mechanism of this radioresistance is still unclear. This study aimed to investigate the effect of radiation on the levels of signal transducer and activator of transcription 1 (STAT1) in mammospheres of cancer-initiating cells and monolayer cultures of MCF-7 cells. We isolated CD44(+)/CD24(-/low) cancer-initiating cells from MCF-7 cells and propagated them as mammospheres. Next we used realtime quantitative reverse-transcriptase polymerase chain reaction to examine the mRNA level of STAT1 in mammospheres of breast cancer-initiating cells and monolayer cultures of MCF-7 cells. The apoptosis rate and surviving fraction using clonogenic assays was observed after treating the cells with a STAT1 inhibitor. After irradiation, the STAT1 level in the mammospheres was higher than that in the monolayer cultures. STAT1 inhibitor treatment did not cause significant changes in the apoptosis rate and surviving fraction in the MCF-7 monolayer cultures. However, the inhibitor treatment caused significant differences in the apoptosis rate and surviving fraction in mammospheres. Our study provides the first evidence that STAT1 signaling contributes to radioresistance in breast cancer-initiating cells and reveals STAT1 as a promising target to reduce radioresistance and enhance the efficacy of radiotherapy for breast cancer.

• Authors: Jun-Fang Zhan, Long-Hua Chen, Ya-Wei Yuan, Guo-Zhu Xie, Ai-Min Sun, Ying Liu, Zhi-Xian Chen
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 236 Issue 4 Pg. 418-22 (Apr 01 2011) ISSN: 1535-3699 [Electronic] England
• PMID: 21444368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD24 Antigen
• Hyaluronan Receptors
• STAT1 Transcription Factor
• STAT1 protein, human

Topics

• Apoptosis (radiation effects)
• Breast Neoplasms (immunology, pathology)
• CD24 Antigen (immunology)
• Cell Line, Tumor
• Female
• Flow Cytometry
• Humans
• Hyaluronan Receptors (immunology)
• Radiation Tolerance (physiology)
• STAT1 Transcription Factor (physiology)