کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6175708 1253032 2016 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer
ترجمه فارسی عنوان
اثرات اولیه محرومیت سریع آندروژن بر سرطان پروستات انسان
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی زنان، زایمان و بهداشت زنان
چکیده انگلیسی

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).Patient summaryThis 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Urology - Volume 70, Issue 2, August 2016, Pages 214-218
نویسندگان
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