Oncotarget

Research Papers:

Characterization of the release and biological significance of cell-free DNA from breast cancer cell lines

Wei Wang, Peng Kong, Ge Ma, Li Li, Jin Zhu, Tiansong Xia, Hui Xie, Wenbin Zhou and Shui Wang _

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Oncotarget. 2017; 8:43180-43191. https://doi.org/10.18632/oncotarget.17858

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Abstract

Wei Wang1,*, Peng Kong1,*, Ge Ma1, Li Li1, Jin Zhu1, Tiansong Xia1, Hui Xie1, Wenbin Zhou1 and Shui Wang1

1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China

*These authors have contributed equally to this work

Correspondence to:

Shui Wang, email: ws0801@hotmail.com

Wenbin Zhou, email: zhouwenbin_1984@foxmail.com

Keywords: breast cancer, cell-free DNA, circulating tumor DNA, biological significance

Received: January 23, 2017    Accepted: April 14, 2017    Published: May 15, 2017

ABSTRACT

In breast cancer, cell-free DNA (cfDNA) has been proven to be a diagnostic and prognostic biomarker. However, there have been few studies on the origin and biological significance of cfDNA. In this study, we assessed the release pattern of cfDNA from breast cancer cell lines under different culture conditions and investigated the biological significance of cfDNA. The cfDNA concentration increased rapidly (6 h) after passage, decreased gradually, and was then maintained at a relatively stable level after 24 h. In addition, the cfDNA concentration did not correlate with the amount of apoptotic and necrotic cells. Interestingly, if more cells were in the G1 phase, more cfDNA was detected (p < 0.01) and the cfDNA concentration correlated positively with the percent of cells in the G1 phase (p < 0.05). We observed that cells could release cfDNA actively, but not exclusively, via exosomes. Furthermore, we showed that cfDNA could stimulate hormone receptor-positive breast cancer cell proliferation by activating the TLR9-NF-κB-cyclin D1 pathway. In conclusion, cfDNA is released from breast cancer mainly by active secretion, and cfDNA could stimulate proliferation of breast cancer cells.


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