title: Overexpression and constitutive nuclear localization of cohesin protease Separase protein correlates with high incidence of relapse and reduced overall survival in glioblastoma multiforme.
abstract: 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.
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Malini
authors.initials: M
authors.lastname: Mukherjee
authors.forename: Tiara
authors.initials: T
authors.lastname: Byrd
authors.forename: Vita S
authors.initials: VS
authors.lastname: Brawley
authors.forename: Kevin
authors.initials: K
authors.lastname: Bielamowicz
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Li
authors.forename: Fatima
authors.initials: F
authors.lastname: Merchant
authors.forename: Saurabh
authors.initials: S
authors.lastname: Maitra
authors.forename: Pavel
authors.initials: P
authors.lastname: Sumazin
authors.forename: Greg
authors.initials: G
authors.lastname: Fuller
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kew
authors.forename: David
authors.initials: D
authors.lastname: Sun
authors.forename: Suzanne Z
authors.initials: SZ
authors.lastname: Powell
authors.forename: Nabil
authors.initials: N
authors.lastname: Ahmed
authors.forename: Nenggang
authors.initials: N
authors.lastname: Zhang
authors.forename: Debananda
authors.initials: D
authors.lastname: Pati
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D011379:Prognosis; D012008:Recurrence; D064247:Separase / Q000378:metabolism*; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D064247:Separase