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

Kati Kivinummi, Alfonso Urbanucci, Katri Leinonen, Teuvo L.J. Tammela, Matti Annala, William B Isaacs, G. Steven Bova, Matti Nykter, Tapio Visakorpi

Research output: Contribution to journalArticle

Abstract

Although second generation endocrine therapies have significantly improved survival, castration-resistant prostate cancer (CRPC) cells are eventually able to escape available hormonal treatments due to reactivation of androgen receptor (AR) signaling. Identification of novel, non-classical and druggable AR-target genes may provide new approaches to treat CRPC. Our previous analyses suggested that Aurora kinase A (AURKA) is regulated by androgens in prostate cancer cells that express high levels of AR. Here, we provide further evidence that AURKA is significantly overexpressed in AR-positive CRPC samples carrying amplification of AR gene and/or expressing AR in high levels. We also demonstrate androgen-induced AR binding in the intronic region of AURKA. The expression of AURKA is increased upon androgen stimulation in LNCaP-ARhi cells that express high levels of AR. The growth of the cells was also significantly inhibited by an AURKA specific inhibitor, alisertib (MLN8237). Together, these findings suggest that the expression of AURKA is regulated by androgen in prostate cancer cells that highly express AR, emphasizing its potential as a therapeutic target in patients with CRPC.

Original languageEnglish (US)
Article number17978
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Aurora Kinase A
Castration
Androgen Receptors
Androgens
Prostatic Neoplasms
Genes
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Kivinummi, K., Urbanucci, A., Leinonen, K., Tammela, T. L. J., Annala, M., Isaacs, W. B., ... Visakorpi, T. (2017). The expression of AURKA is androgen regulated in castration-resistant prostate cancer. Scientific Reports, 7(1), [17978]. https://doi.org/10.1038/s41598-017-18210-3

The expression of AURKA is androgen regulated in castration-resistant prostate cancer. / Kivinummi, Kati; Urbanucci, Alfonso; Leinonen, Katri; Tammela, Teuvo L.J.; Annala, Matti; Isaacs, William B; Bova, G. Steven; Nykter, Matti; Visakorpi, Tapio.

In: Scientific Reports, Vol. 7, No. 1, 17978, 01.12.2017.

Research output: Contribution to journalArticle

Kivinummi, K, Urbanucci, A, Leinonen, K, Tammela, TLJ, Annala, M, Isaacs, WB, Bova, GS, Nykter, M & Visakorpi, T 2017, 'The expression of AURKA is androgen regulated in castration-resistant prostate cancer', Scientific Reports, vol. 7, no. 1, 17978. https://doi.org/10.1038/s41598-017-18210-3
Kivinummi, Kati ; Urbanucci, Alfonso ; Leinonen, Katri ; Tammela, Teuvo L.J. ; Annala, Matti ; Isaacs, William B ; Bova, G. Steven ; Nykter, Matti ; Visakorpi, Tapio. / The expression of AURKA is androgen regulated in castration-resistant prostate cancer. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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