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Correlation between low-level expression of the tumor suppressor gene TAp73 and the chemoresistance of human glioma stem cells

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Abstract

Objective

Glioma stem cells (GSCs) are regarded as the root of glioma growth and recurrence. Chemoresistance is one of the characteristics of GSCs that increases the difficulties in eradicating the cells by anticancer drugs.

Purpose

The objective of this study is to investigate the correlation between expression of the tumor suppressor gene TAp73 and the chemoresistance of human GSCs.

Methods

MTT and tumor sphere formation assays were used to analyze the chemoresistance phenotype of GSCs derived from primary human glioma specimens under cisplatin exposure. Reverse transcription real-time PCR was applied for assaying mRNA levels of TAp73. Protein levels of TAp73, p21, Bax, and cleared caspase 3 were assayed by western blot. Cell apoptosis was analyzed by flow cytometry after the annexin V fluorescence staining.

Results

GSCs exhibited increased chemoresistance compared to differentiated glioma cells (DGCs) derived from the same tumor specimen. The expression of TAp73 was lower in GSCs and was not sensitive to cisplatin treatment as compared to DGCs. Overexpression of TAp73 by transfection increased the apoptosis of GSCs in the presence of cisplatin and reduced the chemoresistance of GSC. TAp73 knockdown by siRNA in DGCs reduced cisplatin-induced apoptosis and increased the resistance to cisplatin.

Conclusion

These findings indicate that TAp73 silencing is hallmark of GSC to maintain their chemoresistance phenotype. Thus, targeting TAp73 may provide a novel strategy to eradicating GSCs.

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Acknowledgments

The authors thank Dr. Ji Ming Wang (Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA) for reviewing the manuscript. This project was supported by the grants from the National Natural Science Foundation of China (NSFC, No. 30873034 and 30973493).

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Authors and Affiliations

  1. Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Xiaogang Hu, Peiyuan Xia, Fengjun Sun & Jianhong Chen

  2. Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Nan Wu

  3. Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Sicang Yu

  4. Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Sicang Yu

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  1. Xiaogang Hu
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  3. Peiyuan Xia
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  4. Sicang Yu
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  5. Fengjun Sun
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Correspondence to Jianhong Chen.

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Hu, X., Wu, N., Xia, P. et al. Correlation between low-level expression of the tumor suppressor gene TAp73 and the chemoresistance of human glioma stem cells. Cancer Chemother Pharmacol 69, 1205–1212 (2012). https://doi.org/10.1007/s00280-012-1823-0

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  • DOI: https://doi.org/10.1007/s00280-012-1823-0

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