Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer.

Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer.
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DOI:
10.1038/sj.bjc.6601127
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发表时间:
2003-08-04
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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本研究检测了来自51名患者的102例配对激素敏感和耐药肿瘤中雄激素受体(AR)基因扩增和蛋白表达。AR基因扩增和X染色体拷贝数通过荧光原位杂交进行评估,蛋白质表达通过免疫组织化学进行评估。对所有肿瘤进行PSA蛋白表达染色。与来自同一患者的匹配的激素敏感性肿瘤(2%,48例中的1例)相比,在激素抵抗发展后,显着更多的肿瘤显示AR扩增(20%,49例中的10例)(P = 0.0085)。AR表达水平在耐药肿瘤中显著高于来自同一患者的匹配的耐药敏感肿瘤(130,四分位数范围,55 - 167 vs 94.5,四分位数范围,55 - 120,P = 0.019)。AR表达水平在AR扩增和不扩增的耐药肿瘤中没有显著差异。然而,随着成对肿瘤中AR扩增的发展,AR表达增加。雄激素抵抗期间AR基因扩增和/或AR蛋白表达增加的速率太低,不能完全解释雄激素抵抗的发展。调节AR或其他信号通路功能的替代机制必须被视为前列腺耐药发展的关键因素。
This study examined androgen receptor (AR) gene amplification and protein expression in 102 matched paired hormone sensitive and resistant tumours from 51 patients. AR gene amplification and X chromosome copy number were assessed by fluorescent in situ hybridisation, and protein expression was assessed by immunohistochemistry. All tumours were stained for PSA protein expression. Significantly more tumours exhibited AR amplification following the development of hormone resistance (20%, 10 out of 49) compared to matched hormone-sensitive tumours from the same patient (2%, one out of 48) (P=0.0085). The level of AR expression was significantly higher in hormone-resistant tumours compared to matched hormone-sensitive tumours from the same patient (130, interquartile range, 55–167 vs 94.5 interquartile range, 55–120, P=0.019). AR expression levels in hormone-resistant tumours with and without AR amplification were not significantly different. However, an increase in AR expression was seen with the development of AR amplification in paired tumours. The rate of AR gene amplification and/or an increase in AR protein expression during androgen resistant is too low to wholly explain the development of androgen resistance. Alternative mechanisms for modulating the function of the AR, or other signalling pathways, must be considered as key factors in the development of hormone-resistant prostate.
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期刊: NATURE GENETICS
影响因子: 30.8
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影响因子: 4.1
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