Journal of Neuro-Oncology

, Volume 119, Issue 1, pp 27–35 | Cite as

Overexpression and constitutive nuclear localization of cohesin protease Separase protein correlates with high incidence of relapse and reduced overall survival in glioblastoma multiforme

  • Malini Mukherjee
  • Tiara Byrd
  • Vita S. Brawley
  • Kevin Bielamowicz
  • Xiao-Nan Li
  • Fatima Merchant
  • Saurabh Maitra
  • Pavel Sumazin
  • Greg Fuller
  • Yvonne Kew
  • David Sun
  • Suzanne Z. Powell
  • Nabil M. Ahmed
  • Nenggang Zhang
  • Debananda Pati
Laboratory Investigation

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.

Keywords

Separase Espl1 GBM 

Supplementary material

11060_2014_1458_MOESM1_ESM.doc (60 kb)
Supplementary material 1 (DOC 59 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Malini Mukherjee
    • 1
    • 3
  • Tiara Byrd
    • 1
    • 2
    • 3
  • Vita S. Brawley
    • 1
    • 2
    • 3
  • Kevin Bielamowicz
    • 2
    • 3
  • Xiao-Nan Li
    • 1
    • 3
    • 5
  • Fatima Merchant
    • 6
  • Saurabh Maitra
    • 7
  • Pavel Sumazin
    • 1
    • 3
  • Greg Fuller
    • 8
  • Yvonne Kew
    • 9
  • David Sun
    • 9
  • Suzanne Z. Powell
    • 9
  • Nabil M. Ahmed
    • 1
    • 2
    • 3
    • 5
    • 9
  • Nenggang Zhang
    • 1
    • 5
  • Debananda Pati
    • 1
    • 3
    • 4
    • 5
  1. 1.Texas Children’s Cancer CenterBaylor College of MedicineHoustonUSA
  2. 2.Center for Cell and Gene TherapyBaylor College of MedicineHoustonUSA
  3. 3.Department of Pediatric Hematology/OncologyBaylor College of MedicineHoustonUSA
  4. 4.Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA
  5. 5.The Dan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonUSA
  6. 6.Department of Engineering TechnologyUniversity of HoustonHoustonUSA
  7. 7.Bauer College of Business, University of HoustonHoustonUSA
  8. 8.Department of PathologyMD Anderson Cancer CenterHoustonUSA
  9. 9.Methodist Hospital Research InstituteHoustonUSA

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