前列腺癌
雄激素受体
雄激素剥夺疗法
下调和上调
医学
雄激素
前列腺切除术
癌症研究
转录组
内分泌学
内科学
TMPRS2型
前列腺
基因表达
癌症
基因
生物
激素
遗传学
疾病
2019年冠状病毒病(COVID-19)
传染病(医学专业)
作者
Greg L. Shaw,Hayley C. Whitaker,Marie Corcoran,Mark J. Dunning,Hayley J. Luxton,Jonathan Kay,Charles E. Massie,Jodi L. Miller,Alastair Lamb,Helen Ross-Adams,Roslin Russell,Adam W Nelson,Matthew Eldridge,Andy G. Lynch,Antonio Ramos-Montoya,Ian G. Mills,Angela E. Taylor,Wiebke Arlt,Nimish Shah,Anne Y. Warren,David E. Neal
标识
DOI:10.1016/j.eururo.2015.10.042
摘要
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). 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.
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