Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas

  • Authors:
    • Carsten Hagemann
    • Jelena Anacker
    • Stefanie Gerngras
    • Siglinde Kühnel
    • Harun M. Said
    • Rajnikant Patel
    • Ulrike Kämmerer
    • Dirk Vordermark
    • Klaus Roosen
    • Giles Hamilton Vince
  • View Affiliations

  • Published online on: August 1, 2008     https://doi.org/10.3892/or_00000007
  • Pages: 301-308
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Abstract

Patients with autosomal recessive primary microcephaly have a small but architecturally normal brain containing a reduced number of neurons. Microcephalin and ASPM are two of the genes causing this disease. Both are centrosomal proteins involved in cell cycle regulation. Whereas microcephalin is a component of the DNA damage response and a repressor of telomerase function, ASPM is required for the proper formation of a central mitotic spindle and ensures symmetric, proliferative divisions of neuro-epithelial cells. Both proteins are also involved in the regulation of tumor growth. Microcephalin expression is reduced in breast cancer cell lines and human tumors of the ovary and prostate. Reduction in microcephalin mRNA expression correlates with increased chromosomal instability. ASPM mRNA is overexpressed in transformed human cell lines and tumors, and its increased expression is positively associated with proliferation of glioblastoma cells. Glioblastomas are the most prevalent malignant brain tumors in adults, characterized by increased invasiveness, an aggressive local growth pattern and short survival periods of patients. In this study, we analysed the expression of microcephalin mRNA and ASPM mRNA and protein in a panel of 15 glioblastomas and 15 astrocytoma WHO grade II by semi-quantitative RT-PCR, Western blotting and immunohistochemistry. Whereas microcephalin expression did not seem to be altered during glioma development, there was a clear increase in ASPM mRNA and protein expression that corresponded with the WHO grade of the tumor. Our findings are significant as the expression of ASPM may be used as a marker for glioma malignancy and represents a potential therapeutic target.

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August 2008
Volume 20 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Hagemann C, Anacker J, Gerngras S, Kühnel S, Said HM, Patel R, Kämmerer U, Vordermark D, Roosen K, Vince GH, Vince GH, et al: Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas. Oncol Rep 20: 301-308, 2008
APA
Hagemann, C., Anacker, J., Gerngras, S., Kühnel, S., Said, H.M., Patel, R. ... Vince, G.H. (2008). Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas. Oncology Reports, 20, 301-308. https://doi.org/10.3892/or_00000007
MLA
Hagemann, C., Anacker, J., Gerngras, S., Kühnel, S., Said, H. M., Patel, R., Kämmerer, U., Vordermark, D., Roosen, K., Vince, G. H."Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas". Oncology Reports 20.2 (2008): 301-308.
Chicago
Hagemann, C., Anacker, J., Gerngras, S., Kühnel, S., Said, H. M., Patel, R., Kämmerer, U., Vordermark, D., Roosen, K., Vince, G. H."Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas". Oncology Reports 20, no. 2 (2008): 301-308. https://doi.org/10.3892/or_00000007