IN-VIVO AMPLIFICATION OF THE ANDROGEN RECEPTOR GENE AND PROGRESSION OF HUMAN PROSTATE-CANCER
IN-VIVO AMPLIFICATION OF THE ANDROGEN RECEPTOR GENE AND PROGRESSION OF HUMAN PROSTATE-CANCER
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DOI：
10.1038/ng0495-401
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发表时间：
1995-04-01
期刊：
影响因子：
30.8
通讯作者：
KALLIONIEMI, OP
中科院分区：
文献类型：
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作者：
VISAKORPI, T;HYYTINEN, E;KALLIONIEMI, OP
在体外，扩增基因的过度表达通常与获得对癌症治疗药物的耐药性有关。我们已经确定了人类前列腺癌内分泌治疗失败的体内类似的分子机制，涉及雄激素受体（AR）基因的扩增。比较基因组杂交显示，Xq11-q13区域（位置）的扩增在雄激素剥夺治疗期间复发的肿瘤中很常见。我们发现23例复发肿瘤中有7例（30%）存在高水平的AR扩增，但在治疗前取自同一患者的标本中均未发现。我们的研究结果表明，在雄激素剥夺治疗期间，AR扩增通过促进肿瘤细胞在低雄激素浓度下的生长而出现。
Overexpression of amplified genes is often associated with the acquisition of resistance to cancer therapeutic agents in vitro. We have identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene. Comparative genomic hybridization shows that amplification of the Xq11-q13 region (the location), is common in tumours recurring during androgen deprivation therapy. We found high-level AR amplification in seven of 23 (30%) recurrent tumours, but in none of the specimens taken from the same patients prior to therapy. Our results suggest that AR amplification emerges during androgen deprivation therapy by facilitating tumour cell growth in low androgen concentrations.