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前列腺癌细胞系和良性前列腺增生组织在体外的5α-还原酶表达

5 alpha-reductase expression by prostate cancer cell lines and benign prostatic hyperplasia in vitro.

作者信息

Smith C M, Ballard S A, Worman N, Buettner R, Masters J R

机构信息

University College London, Institute of Urology and Nephrology, Research Laboratories, United Kingdom.

出版信息

J Clin Endocrinol Metab. 1996 Apr;81(4):1361-6. doi: 10.1210/jcem.81.4.8636334.

Abstract

5 alpha-reductase (5 alpha R) activity in two human prostate cancer cell lines was compared to that in benign prostatic hyperplasia (BPH) tissue and COS cells transfected with and expressing the human genes for 5 alpha-reductase type 1 (5 alpha R1) and type 2 (5 alpha R2). Comparisons were based on pH profiles and sensitivities to selective inhibitors of 5 alpha-reductase In the cancer lines, activity was greatest over the pH range 7-8, compared to a sharp peak of activity between pH 5-5.5 in BPH tissue and COS cells expressing 5 alpha R2. Finasteride and SKF105,657 were potent inhibitors of 5 alpha-reductase activity in BPH tissue and COS cells expressing 5 alpha R2, but weak inhibitors in the cancer lines and in COS cells expressing 5 alpha R1. In contrast, UK117,026 was a more potent inhibitor of 5 alpha-reductase activity in the prostate cancer cell lines and in COS cells expressing 5 alpha R1. These data indicate that human prostate cancer cell lines express 5 alpha-reductase activity similar to that in COS cells transfected with 5 alpha R1, but different from that in BPH tissue. This may be a consequence of in vitro culture. Alternatively, it may reflect a change occurring as a result of neoplastic transformation in which case it will be important to select appropriate inhibitors in the clinic.

摘要

将两个人前列腺癌细胞系中的5α-还原酶(5αR)活性与良性前列腺增生(BPH)组织以及转染并表达人1型5α-还原酶(5αR1)和2型5α-还原酶(5αR2)基因的COS细胞中的活性进行了比较。比较基于pH谱以及对5α-还原酶选择性抑制剂的敏感性。在癌细胞系中,pH值在7 - 8范围内活性最高,相比之下,BPH组织和表达5αR2的COS细胞在pH 5 - 5.5之间有一个活性尖峰。非那雄胺和SKF105,657是BPH组织和表达5αR2的COS细胞中5α-还原酶活性的有效抑制剂,但在癌细胞系和表达5αR1的COS细胞中是弱抑制剂。相比之下,UK117,026在前列腺癌细胞系和表达5αR1的COS细胞中是5α-还原酶活性更强的抑制剂。这些数据表明,人前列腺癌细胞系表达的5α-还原酶活性与转染5αR1的COS细胞中的活性相似,但与BPH组织中的不同。这可能是体外培养的结果。或者,它可能反映了肿瘤转化导致的变化,在这种情况下,在临床上选择合适的抑制剂将很重要。

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