Separase, an
enzyme that cleaves the chromosomal
cohesin during mitosis, is overexpressed in a wide range of human epithelial
cancers of breast, bone and prostate (Meyer et al., Clin
Cancer Res 15(8):2703-2710, 2009). Overexpression of
Separase in animal models results in
aneuploidy and
tumorigenesis. We have examined the expression and localization of
Separase protein in adult and pediatric
glioblastoma and normal brain specimens. Immunofluorescence microscopy and Western blot analysis showed significant overexpression of
Separase in all adult and a subset of pediatric
glioblastoma cells.
Tumor status and patient survival strongly correlate with the mislocalization of
Separase into the nucleus throughout all stages of the cell cycle. Unlike exclusively nuclear localization in mitotic control cells,
glioblastoma samples have a significantly higher number of resting (interphase) cells with strong nuclear
Separase staining. Additionally, patient survival analysis demonstrated a strong correlation between overexpression of
Separase protein in adult
glioblastoma and a high incidence of relapse and reduced overall survival. These results further strengthen our hypothesis that
Separase is an oncogene whose overexpression induces
tumorigenesis, and indicate that
Separase overexpression and aberrant nuclear localization are common in many
tumor types and may predict outcome in some human
malignancies.