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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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The expression of AURKA is androgen regulated in castration-resistant prostate cancer

Kati Kivinummi1, Alfonso Urbanucci2,3,4,5,6, Katri Leinonen2

  • 1BioMediTech Institute, Faculty of Medicine and Life Sciences, University of Tampere, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland. kati.kivinummi@uta.fi.

Scientific Reports
|December 23, 2017
PubMed

Insights

Castration-resistant prostate cancer (CRPC) cells reactivate androgen receptor (AR) signaling. Targeting Aurora kinase A (AURKA), an AR-regulated gene, shows promise for treating advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Castration-resistant prostate cancer (CRPC) remains a significant clinical challenge.
  • Reactivation of androgen receptor (AR) signaling drives CRPC progression despite endocrine therapies.
  • Novel therapeutic targets are needed to overcome treatment resistance.

Purpose of the Study:

  • To investigate Aurora kinase A (AURKA) as a potential therapeutic target in CRPC.
  • To elucidate the regulatory relationship between AR signaling and AURKA expression in prostate cancer.

Main Methods:

  • Analysis of AURKA expression in AR-positive CRPC patient samples.
  • Chromatin immunoprecipitation assays to detect AR binding to the AURKA gene.
  • Androgen stimulation experiments in LNCaP-ARhi cells.
  • Inhibition of AURKA using alisertib (MLN8237) and assessment of cell growth.

Main Results:

  • AURKA is significantly overexpressed in AR-positive CRPC with high AR levels or AR gene amplification.
  • Androgen stimulation induces AR binding to an intronic region of the AURKA gene.
  • AURKA expression increases upon androgen stimulation in LNCaP-ARhi cells.
  • Alisertib significantly inhibits the growth of prostate cancer cells.

Conclusions:

  • AURKA expression is androgen-regulated in prostate cancer cells with high AR expression.
  • AURKA represents a potential therapeutic target for patients with CRPC.
  • Targeting AURKA may offer a new strategy to treat advanced prostate cancer.

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