期刊
EUROPEAN UROLOGY
卷 70, 期 2, 页码 214-218出版社
ELSEVIER
DOI: 10.1016/j.eururo.2015.10.042
关键词
Prostate cancer; Androgen receptor; Castration; Clinical trial; Immunohistochemistry; Gene transcription
资金
- Academy of Medical Sciences
- National Institute for Health Research
- Cancer Research UK
- National Cancer Research
- MRC [G116/172, G0900567, MR/L00156X/1, G0801473] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL11-Lamb] Funding Source: researchfish
- Medical Research Council [G116/172, MR/L00156X/1, G0801473, G0900567] Funding Source: researchfish
- National Institute for Health Research [CL-2012-14-003, CL-2009-14-006] Funding Source: researchfish
- Prostate Cancer UK [G2012/50, PA14-022] Funding Source: researchfish
- The Urology Foundation [RESCH1302] Funding Source: researchfish
- Versus Arthritis
- Cancer Research UK [20406] Funding Source: researchfish
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 alpha-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). Patient summary: This first-in-man study defines the rapid gene expression changes taking place in prostate cancer (PCa) following castration. Expression levels of the genes that the androgen receptor regulates are predictive of treatment outcome. Upregulation of oestrogen receptor 1 is a mechanism by which PCa cells may survive despite castration. (C) 2015 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BY license.
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