Amplification of the androgen receptor may not explain the development of androgen-independent prostate cancer
Amplification of the androgen receptor may not explain the development of androgen-independent prostate cancer
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DOI：
10.1046/j.1464-410x.2001.02350.x
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发表时间：
2001-10-01
影响因子：
4.5
通讯作者：
Bartlett, JMS
中科院分区：
文献类型：
--
作者：
Edwards, J;Krishna, NS;Bartlett, JMS
目的探讨雄激素受体(AR)基因扩增和X染色体异型在抗雄激素抵抗性前列腺癌发生发展中的作用。患者及方法选择20例对雄激素剥夺治疗抵抗的前列腺癌患者进行研究。检索抗雄激素治疗前后肿瘤患者的记录以及完整的临床随访记录。 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，使用AR基因位点Xq11-13处的标记探针和X染色体的标记α卫星探针。两名独立观察者对三个肿瘤区域至少 20 个细胞核进行评分。 结果 在激素复发前后，分别有 7 个 (35%) 和 11 个 (55%) 肿瘤报告 X 染色体畸形，7 个 (35%) 和 13 个 (65%) 肿瘤的 AR 基因拷贝数分别增加，1 个 (5%) 和 3 个 (15%) 肿瘤分别检测到 AR 基因扩增。原发性肿瘤中AR拷贝数的增加和AR扩增均不排除对雄激素剥夺疗法的生物反应。结论AR基因扩增率太低，不能单独负责抗雄激素抵抗性前列腺癌的发生。此外，对雄激素剥夺疗法有反应的原发性肿瘤中存在扩增的 AR 和 X 染色体异体细胞，这表明 AR 基因拷贝数的增加并不能阻止肿瘤对该疗法做出反应。因此，在了解为什么如此多的患者复发这种疾病之前，必须研究可能导致激素难治性前列腺癌的其他机制。
Objective To examine the role of androgen receptor (AR) gene amplification and aneusomy of the X chromosome in the development of antiandrogen-resistant prostate cancer.Patients and methods Twenty patients with prostate cancer resistant to androgen-deprivation therapy were selected for study. The records of patients with tumours before and after antiandrogen therapy, and with a full clinical follow-up, were retrieved. AR gene amplification and X chromosome copy number were assessed by fluorescence in situ hybridization using a labelled probe at locus Xq11-13 for the AR gene and a labelled a-satellite probe for the X chromosome. At least 20 nuclei were scored over three tumour areas by two independent observers.Results Aneusomy of the X chromosome was reported respectively in seven (35%) and 11 (55%) tumours before and after hormone relapse, the AR gene copy number was increased in seven (35%) and 13 (65%), respectively, and AR gene amplification was detected in one (5%) and three (15%), respectively. Neither increased AR copy number nor AR amplification in primary tumours precluded a biological response to androgen-deprivation therapy.Conclusion The rate of AR gene amplification is too low to be solely responsible for the development of antiandrogen-resistant prostate cancer. Also, the presence of amplified AR and cells aneusomic for the X chromosome in primary tumours that respond to androgen-deprivation therapy suggests that an increase in AR gene copy number does not prevent a tumour from responding to this therapy. Therefore other mechanisms which could cause hormone-refractory prostate cancer must be investigated before it is understood why so many patients relapse with this disease.