Cellular Oncology

, Volume 35, Issue 2, pp 85–93 | Cite as

Expression of the SEPT9_i4 isoform confers resistance to microtubule-interacting drugs

  • Alex D. Chacko
  • Simon S. McDade
  • Severine Chanduloy
  • Stewart W. Church
  • Richard Kennedy
  • John Price
  • Peter A. Hall
  • S. E. Hilary Russell
Original Paper

Abstract

Background

The evolutionarily conserved septin family of genes encode GTP binding proteins involved in a variety of cellular functions including cytokinesis, apoptosis, membrane dynamics and vesicle trafficking. Septin proteins can form hetero-oligomeric complexes and interact with other proteins including actin and tubulin. The human SEPT9 gene on chromosome 17q25.3 has a complex genomic architecture with 18 different transcripts that can encode 15 distinct polypeptides. Two distinct transcripts with unique 5′ ends (SEPT9_v4 and SEPT9_v4*) encode the same protein. In tumours the ratio of these transcripts changes with elevated levels of SEPT9_v4* mRNA, a transcript that is translated with enhanced efficiency leading to increased SEPT9_i4 protein.

Methods

We have examined the effect of over-expression of SEPT9_i4 on the dynamics of microtubule polymer mass in cultured cells.

Results

We show that the microtubule network in SEPT9_i4 over-expressing cells resists disruption by paclitaxel or cold incubation but also repolymerises tubulin more slowly after microtubule depolymerisation. Finally we show that SEPT9_i4 over-expressing cells have enhanced survival in the presence of clinically relevant microtubule acting drugs but not after treatment with DNAinteracting agents.

Conclusions

Given that SEPT9 over-expression is seen in diverse tumours and in particular ovarian and breast cancer, such data indicate that SEPT9_v4 expression may be clinically relevant and contribute to some forms of drug resistance.

Keywords

Septin SEPT9 Microtubules Drug resistance 

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Copyright information

© International Society for Cellular Oncology 2012

Authors and Affiliations

  • Alex D. Chacko
    • 1
  • Simon S. McDade
    • 1
  • Severine Chanduloy
    • 1
  • Stewart W. Church
    • 1
  • Richard Kennedy
    • 1
  • John Price
    • 2
  • Peter A. Hall
    • 3
    • 4
  • S. E. Hilary Russell
    • 1
  1. 1.Centre for Cancer Research and Cell BiologyQueen’s University BelfastBelfastUK
  2. 2.Department of GynaecologyTower Block, Belfast City HospitalBelfastUK
  3. 3.Departments of Molecular Oncology and Pathology & Laboratory MedicineKing Faisal Specialist Hospital & Research CentreRiyadhSaudi Arabia
  4. 4.College of Medicine, Alfaisal UniversityRiyadhSaudi Arabia

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