The early effects of rapid androgen deprivation on human prostate cancer

The androgen receptor (AR) is the dominant growth factor in prostate cancer. Understanding how it regulates the human transcriptome is of paramount importance. The early effects of castration on human prostate cancer have not previously been studied. In this study 27 patients were medically castrated with degarelix seven days before radical prostatectomy. Resected tumour was compared with matched controlled untreated prostate cancer tissue by means of mass spectrometry, immunohistochemistry and gene expression array (validated by RT-PCR). All patients had castrate levels of serum androgen with reduced levels of intra-prostatic androgen at prostatectomy. Differential expression of known androgen regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5) was observed. We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of AMACR expression and three other genes (FAM129A, RAB27A and KIAA0101) was confirmed. Up-regulation of oestrogen receptor alpha (ESR1) expression was observed in malignant epithelia. This was associated with differential expression of ESR1 regulated genes and correlated with proliferation (Ki67 expression).

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