Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas.
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.
Hagemann
Carsten
C
Department of Neurosurgery, University of Würzburg, D-97080 Würzburg, Germany. hagemann_c@klinik.uni-wuerzburg.de
Anacker
Jelena
J
Gerngras
Stefanie
S
Kühnel
Siglinde
S
Said
Harun M
HM
Patel
Rajnikant
R
Kämmerer
Ulrike
U
Vordermark
Dirk
D
Roosen
Klaus
K
Vince
Giles Hamilton
GH
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005808:Genes, Recessive; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C467202:ASPM protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger