The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer.
Shaw, Greg L
Nelson, Adam W
Mills, Ian G
Taylor, Angela E
Neal, David E
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Shaw, G. L., Whitaker, H., Corcoran, M., Dunning, M., Luxton, H., Kay, J., Massie, C., et al. (2016). The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer.. European Urology, 70 (2), 214-218. https://doi.org/10.1016/j.eururo.2015.10.042
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).
Androgen receptor, Castration, Clinical trial, Gene transcription, Immunohistochemistry, Prostate cancer, Estrogen Receptor alpha, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hormone Antagonists, Humans, Immunohistochemistry, Male, Oligopeptides, Preoperative Care, Prostate, Prostatectomy, Prostatic Neoplasms, Receptors, Androgen, Spectrum Analysis
THE PROSTATE CANCER CHARITY (G2012-50)
PROSTATE CANCER UK (PA14-022)
External DOI: https://doi.org/10.1016/j.eururo.2015.10.042
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252506
Creative Commons Attribution 4.0 International License
Licence URL: http://creativecommons.org/licenses/by/4.0/