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Expression of andro...
Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival
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- Hörnberg, Emma (författare)
- Umeå universitet,Patologi
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- Bovinder Ylitalo, Erik (författare)
- Umeå universitet,Patologi
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- Crnalic, Sead (författare)
- Umeå universitet,Ortopedi
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- Antti, Henrik (författare)
- Umeå universitet,Kemiska institutionen
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- Stattin, Pär (författare)
- Umeå universitet,Urologi och andrologi
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- Widmark, Anders (författare)
- Umeå universitet,Onkologi
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- Bergh, Anders (författare)
- Umeå universitet,Patologi
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- Wikström, Pernilla (författare)
- Umeå universitet,Patologi
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(creator_code:org_t)
- 2011-04-28
- 2011
- Engelska.
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4, s. e19059-
- Relaterad länk:
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https://umu.diva-por... (primary) (Raw object)
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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-naı¨ve (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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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