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iASPP and chemoresistance in ovarian cancers: effects on paclitaxel-mediated mitotic catastrophe

Lili Jiang1, Michelle K Y Siu, Oscar G W Wong

  • 1Department of Pathology, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 20, 2011
PubMed
Abstract

Insights

Overexpression of iASPP in ovarian cancer correlates with poor prognosis and chemoresistance. Inhibiting iASPP may enhance chemotherapy effectiveness by promoting mitotic catastrophe.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Inhibitor of Apoptosis, Stress-Sensitive (iASPP) is a regulator of p53-mediated apoptosis.
  • The role of iASPP in ovarian cancer and its impact on chemotherapy sensitivity remain largely unexplored.

Purpose of the Study:

  • To investigate the expression profile of iASPP in ovarian epithelial tumors.
  • To determine the effect of iASPP on paclitaxel chemosensitivity in ovarian cancer.

Main Methods:

  • Examined iASPP expression and amplification in 203 ovarian cancer samples and 17 cell lines using immunohistochemistry, qPCR, and immunoblotting.
  • Correlated iASPP levels with clinicopathologic parameters and patient survival.
  • Analyzed changes in proliferation, mitotic catastrophe, and apoptosis in ovarian cancer cells with varying p53 status following paclitaxel treatment.

Main Results:

  • Significantly increased iASPP protein and mRNA expression were observed in ovarian cancer tissues and cell lines.
  • High iASPP expression was associated with clear cell carcinoma, chemoresistance to carboplatin and paclitaxel, and shorter overall and disease-free survival.
  • iASPP overexpression conferred paclitaxel resistance by inhibiting mitotic catastrophe via separase activation in a p53-independent manner, while iASPP knockdown enhanced paclitaxel-induced mitotic catastrophe.

Conclusions:

  • iASPP overexpression is linked to gene amplification in ovarian cancer, predicting poor patient outcomes and chemoresistance.
  • iASPP plays a role in blocking mitotic catastrophe, contributing to therapeutic resistance.
  • iASPP warrants further investigation as a potential prognostic biomarker and therapeutic target in ovarian cancer.

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