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Constitutively active androgen receptor splice variants AR-V3, AR-V7 and AR-V9 are co-expressed in castration-resistant prostate cancer metastases

Kallio, Heini M.L. (författare)
University of Tampere
Hieta, Reija (författare)
University of Tampere
Latonen, Leena (författare)
University of Tampere
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Brofeldt, Anniina (författare)
University of Tampere
Annala, Matti (författare)
University of Tampere
Kivinummi, Kati (författare)
University of Tampere
Tammela, Teuvo L. (författare)
University of Tampere,Tampere University Hospital
Nykter, Matti (författare)
University of Tampere
Isaacs, William B. (författare)
Johns Hopkins University School of Medicine
Lilja, Hans G. (författare)
Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine,University of Tampere,University of Oxford,Memorial Sloan-Kettering Cancer Center
Bova, G. Steven (författare)
University of Tampere
Visakorpi, Tapio (författare)
Tampere University Hospital,University of Tampere
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 (creator_code:org_t)
2018-07-10
2018
Engelska 10 s.
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 119:3, s. 347-356
Relaterad länk:
http://dx.doi.org/10... (free)
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https://www.nature.c...
https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Background: A significant subset of prostate cancer (PC) patients with a castration-resistant form of the disease (CRPC) show primary resistance to androgen receptor (AR)-targeting drugs developed against CRPC. As one explanation could be the expression of constitutively active androgen receptor splice variants (AR-Vs), our current objectives were to study AR-Vs and other AR aberrations to better understand the emergence of CRPC. Methods: We analysed specimens from different stages of prostate cancer by next-generation sequencing and immunohistochemistry. Results: AR mutations and copy number variations were detected only in CRPC specimens. Genomic structural rearrangements of AR were observed in 5/30 metastatic CRPC patients, but they were not associated with expression of previously known AR-Vs. The predominant AR-Vs detected were AR-V3, AR-V7 and AR-V9, with the expression levels being significantly higher in CRPC cases compared to prostatectomy samples. Out of 25 CRPC metastases that expressed any AR variant, 17 cases harboured expression of all three of these AR-Vs. AR-V7 protein expression was highly heterogeneous and higher in CRPC compared to hormone-naïve tumours. Conclusions: AR-V3, AR-V7 and AR-V9 are co-expressed in CRPC metastases highlighting the fact that inhibiting AR function via regions common to all AR-Vs is likely to provide additional benefit to patients with CRPC.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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