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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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March-2015 Volume 46 Issue 3

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International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

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Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

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International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

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Article

Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells

  • Authors:
    • Shaobo Ke
    • Fuxiang Zhou
    • Hui Yang
    • Yuehua Wei
    • Jun Gong
    • Zijie Mei
    • Lin Wu
    • Haijun Yu
    • Yunfeng Zhou
  • View Affiliations / Copyright

    Affiliations: Hubei Key Laboratory of Tumor Biological Behavior, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China
  • Pages: 1051-1058
    |
    Published online on: December 10, 2014
       https://doi.org/10.3892/ijo.2014.2793
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Abstract

The functions of the high mobility group box 1 (HMGB1) in tumor cells include replenishing telomeric DNA and maintaining cell immortality. There is a negative correlation between human telomerase reverse transcriptase (hTERT) and radiosensitivity in tumor cells. Our aim was to elucidate the relationship among HMGB1, telomere homeostasis and radiosensitivity in MCF-7 cells. In this study, we established stably transfected control (MCF-7-NC) and HMGB1 knockdown (MCF-7-shHMGB1) cell lines. The expression of HMGB1 mRNA and the relative telomere length were examined by real-time PCR. Radiosensitivity was detected by clonogenic assay. The protein expressions were determined by western blot analysis. The telomerase activity was detected by PCR-ELISA. Proliferation ability was examined by CCK-8 assay. Cell cycle and apoptosis were examined by flow cytometry. DNA damage foci were detected by immunofluorescence. ShRNA-mediated downregulation of HMGB1 expression increased the radiosensitivity of MCF-7 cells, and reduced the accumulation of hTERT and cyclin D1. Moreover, knockdown of HMGB1 in MCF-7 cells inhibited telomerase activity and cell proliferation, while increasing the extent of apoptosis. Downregulation of HMGB1 modulated telomere homeostasis by changing the level of telomere-binding proteins, such as TPP1 (PTOP), TRF1 and TRF2. This downregulation also inhibited the ATM and ATR signaling pathways. The current data demonstrate that knockdown of HMGB1 breaks telomere homeostasis, enhances radiosensitivity, and suppresses the repair of DNA damage in human breast cancer cells. These results suggested that HMGB1 might be a potential radiotherapy target in human breast cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Ke S, Zhou F, Yang H, Wei Y, Gong J, Mei Z, Wu L, Yu H and Zhou Y: Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells. Int J Oncol 46: 1051-1058, 2015.
APA
Ke, S., Zhou, F., Yang, H., Wei, Y., Gong, J., Mei, Z. ... Zhou, Y. (2015). Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells. International Journal of Oncology, 46, 1051-1058. https://doi.org/10.3892/ijo.2014.2793
MLA
Ke, S., Zhou, F., Yang, H., Wei, Y., Gong, J., Mei, Z., Wu, L., Yu, H., Zhou, Y."Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells". International Journal of Oncology 46.3 (2015): 1051-1058.
Chicago
Ke, S., Zhou, F., Yang, H., Wei, Y., Gong, J., Mei, Z., Wu, L., Yu, H., Zhou, Y."Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells". International Journal of Oncology 46, no. 3 (2015): 1051-1058. https://doi.org/10.3892/ijo.2014.2793
Copy and paste a formatted citation
x
Spandidos Publications style
Ke S, Zhou F, Yang H, Wei Y, Gong J, Mei Z, Wu L, Yu H and Zhou Y: Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells. Int J Oncol 46: 1051-1058, 2015.
APA
Ke, S., Zhou, F., Yang, H., Wei, Y., Gong, J., Mei, Z. ... Zhou, Y. (2015). Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells. International Journal of Oncology, 46, 1051-1058. https://doi.org/10.3892/ijo.2014.2793
MLA
Ke, S., Zhou, F., Yang, H., Wei, Y., Gong, J., Mei, Z., Wu, L., Yu, H., Zhou, Y."Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells". International Journal of Oncology 46.3 (2015): 1051-1058.
Chicago
Ke, S., Zhou, F., Yang, H., Wei, Y., Gong, J., Mei, Z., Wu, L., Yu, H., Zhou, Y."Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells". International Journal of Oncology 46, no. 3 (2015): 1051-1058. https://doi.org/10.3892/ijo.2014.2793
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