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.