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Spy1 Is Frequently Overexpressed in Malignant Gliomas and Critically Regulates the Proliferation of Glioma Cells

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Abstract

Spy1, a member of the Speedy/RINGO family, is a novel activator of cyclin-dependent kinases known to mediate cell cycle progression and cell survival in response to DNA damage. This study focused on the role of Spy1 in glioma oncogenesis. Immunohistochemistry and western blot analysis were performed to examine the expression of Spy1 in human glioma tissues and cell lines. Spy1 was frequently overexpressed in tumor tissues and cultured cells. Our data suggested that Spy1 expression positively correlated with the malignancy of gliomas. Altered expression of Spy1 led to changes in cell cycle processes, cyclin-dependent kinase 2 activity, and p27kip1 protein stabilization, ultimately disrupting cell growth rate. More importantly, high expression of Spy1 was associated with poor prognosis in patients with glioma, suggesting that Spy1 may be a novel independent prognostic predictor of survival for glioma patients. Collectively, this is the first report that Spy1 may play an essential role in the growth processes of human glioma.

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Abbreviations

CDK:

Cyclin-dependent kinase

KPS:

Karnofsky Performance Status

PCNA:

Proliferating cell nuclear antigen

RT-PCR:

Reverse transcriptase polymerase chain reaction

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

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Acknowledgments

We wish to thank Dr. Lisa A. Porter for supplying the Myc-tagged Spy1 construct. This work was supported by the National Basic Research Program of China (973 Program, nos. 2011CB910604 and 2012BC822104), the National Natural Science Foundation of China (nos. 31070723, 81070275, and 81172879), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the College and University Natural Scientific Research Programme of Jiangsu Province (no. 11KJA310002).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical College of Nantong University, Nantong, 226001, People’s Republic of China

    Li Zhang, Aiguo Shen & Chun Cheng

  2. The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China

    Li Zhang, Aiguo Shen & Meijuan Yan

  3. Department of Oncology, Taihe Hospital Affiliated to Hubei University of Medicine, Shiyan, 442000, China

    Qing Ke

  4. Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, People’s Republic of China

    Wei Zhao

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  1. Li Zhang
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  2. Aiguo Shen
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  3. Qing Ke
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  4. Wei Zhao
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  5. Meijuan Yan
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  6. Chun Cheng
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Correspondence to Meijuan Yan or Chun Cheng.

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Li Zhang and Aiguo Shen both contributed equally to this work.

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Zhang, L., Shen, A., Ke, Q. et al. Spy1 Is Frequently Overexpressed in Malignant Gliomas and Critically Regulates the Proliferation of Glioma Cells. J Mol Neurosci 47, 485–494 (2012). https://doi.org/10.1007/s12031-012-9709-5

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  • DOI: https://doi.org/10.1007/s12031-012-9709-5

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