The early effects of rapid androgen deprivation on human prostate cancer
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tumour with matched, controlled, untreated PCa tissue. All patients had levels of serum androgen, with reduced levels of intraprostatic androgen at prostatectomy. We observed differential expression of known androgen-regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of α-methylacyl-CoA racemase expression and three other genes (FAM129A, RAB27A, and KIAA0101) was confirmed. Upregulation of oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia and was associated with differential expression of ESR1-regulated genes and correlated with proliferation (Ki-67 expression).
Date Issued
2016-08-01
Date Acceptance
2015-10-20
Citation
European Urology, 2016, 70 (2), pp.214-218
ISSN
0302-2838
Publisher
Elsevier
Start Page
214
End Page
218
Journal / Book Title
European Urology
Volume
70
Issue
2
Copyright Statement
© 2015 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/26572708
PII: S0302-2838(15)01076-3
Subjects
ALPHA
Androgen receptor
Castration
CASTRATION
Clinical trial
Gene transcription
Immunohistochemistry
Life Sciences & Biomedicine
Prostate cancer
Science & Technology
Urology & Nephrology
Publication Status
Published
Coverage Spatial
Switzerland
Date Publish Online
2015-11-10