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Cited by 498

The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.

Expression of Androgen Receptor Splice Variants in Prostate Cancer Bone Metastases is Associated with Castration-Resistance and Short Survival

Open access
Hörnberg, Emma, Ylitalo, Erik Bovinder, Crnalic, Sead, Antti, Henrik, Stattin, Pär, Widmark, Anders, Bergh, Anders, Wikström, Pernilla·2011·PLoS ONE
DOI 10.1371/journal.pone.0019059
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Abstract

BACKGROUND: Constitutively active androgen receptor variants (AR-V) lacking the ligand binding domain (LBD) may promote the development of castration-resistant prostate cancer (CRPC). The expression of AR-Vs in the clinically most important metastatic site, the bone, has, however, not been well documented. Our aim was therefore to compare levels of AR-Vs in hormone-naive (HN) and CRPC bone metastases in comparison to primary PC and non-malignant prostate tissue, as well as in relation to AR protein expression, whole-genome transcription profiles and patient survival. METHODOLOGY/PRINCIPAL FINDINGS: Hormone-naïve (n = 10) and CRPC bone metastases samples (n = 30) were obtained from 40 patients at metastasis surgery. Non-malignant and malignant prostate samples were acquired from 13 prostatectomized men. Levels of full length AR (ARfl) and AR-Vs termed AR-V1, AR-V7, and AR-V567es mRNA were measured with RT-PCR and whole-genome transcription profiles with an Illumina Beadchip array. Protein levels were examined by Western blotting and immunohistochemistry. Transcripts for ARfl, AR-V1, and AR-V7 were detected in most primary tumors and metastases, and levels were significantly increased in CRPC bone metastases. The AR-V567es transcript was detected in 23% of the CRPC bone metastases only. A sub-group of CRPC bone metastases expressed LBD-truncated AR proteins at levels comparable to the ARfl. Detectable AR-V567es and/or AR-V7 mRNA in the upper quartile, seen in 1/3 of all CRPC bone metastases, was associated with a high nuclear AR immunostaining score, disturbed cell cycle regulation and short survival. CONCLUSIONS/SIGNIFICANCE: Expression of AR-Vs is increased in CRPC compared to HN bone metastases and associated with a particularly poor prognosis. Further studies are needed to test if patients expressing such AR-Vs in their bone metastases benefit more from drugs acting on or down-stream of these AR-Vs than from therapies inhibiting androgen synthesis.

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Metadata

Authors
Hörnberg, E., Ylitalo, E. B., Crnalic, S., Antti, H., Stattin, P., Widmark, A., Bergh, A., & Wikström, P.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-04-28
Volume
6
Issue
4
Pages
e19059
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0019059
OpenAlex
W2114022883
Cited by
498
References
26
FWCI
31.43
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Expression of Androgen Receptor Splice Variants in Prostate Cancer Bone Metastases is Associated with Castration-Resistance and Short Survival. https://app.cochat.ai/papers/10.1371/journal.pone.0019059
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Hörnberg, E., Ylitalo, E. B., Crnalic, S., Antti, H., Stattin, P., Widmark, A., Bergh, A., & Wikström, P. (2011). Expression of Androgen Receptor Splice Variants in Prostate Cancer Bone Metastases is Associated with Castration-Resistance and Short Survival. PLoS ONE. https://doi.org/10.1371/journal.pone.0019059

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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