REGULATION OF PROLIFERATION AND PRODUCTION OF PROSTATE-SPECIFIC ANTIGEN IN ANDROGEN-SENSITIVE PROSTATIC-CANCER CELLS, LNCAP, BY DIHYDROTESTOSTERONE
REGULATION OF PROLIFERATION AND PRODUCTION OF PROSTATE-SPECIFIC ANTIGEN IN ANDROGEN-SENSITIVE PROSTATIC-CANCER CELLS, LNCAP, BY DIHYDROTESTOSTERONE
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DOI：
10.1210/en.136.2.796
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发表时间：
1995-02-01
期刊：
影响因子：
4.8
通讯作者：
KOZLOWSKI, JM
中科院分区：
文献类型：
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作者：
LEE, C;SUTKOWSKI, DM;KOZLOWSKI, JM
LNCaP是雄激素敏感的人前列腺癌细胞系。雄激素对这些细胞的作用的特征在于钟形生长反应和前列腺特异性抗原（PSA）产生的剂量依赖性诱导。本研究旨在进一步了解雄激素对LNCaP的影响。在4天的培养系统中，将细胞培养在补充有10%活性炭剥离的胎牛血清的无酚红RPMI-1640中，双氢睾酮（DHT）浓度范围为0-10（-7）M。在10（-10）M DHT时细胞计数达到峰值水平。这些细胞的PSA分泌直到培养基中的DHT水平达到10（-9）M才显著增加。在较高的DHT浓度下观察到PSA分泌的进行性增加，伴随着细胞增殖的进行性下降。PSA定位的免疫细胞化学分析结果表明，随着DHT浓度的增加，PSA阳性染色的细胞比例也增加。雄激素受体的分析，确定由免疫细胞化学和Western印迹分析，显示在低浓度的DHT和在高浓度的受体蛋白的量增加的核雄激素受体的下降。这些结果表明，雄激素诱导的LNCaP细胞钟形生长反应代表了两种不同的细胞事件的表现，在剂量相关的方式：细胞增殖在低浓度的DHT和PSA的生产增加在高浓度的DHT。
LNCaP is an androgen-sensitive human prostatic cancer cell line. The effect of androgen on these cells is characterized by a bell-shaped growth response and a dose-dependent induction of prostate-specific antigen (PSA) production. The present study was carried out to gain further insight into the effect of androgen on LNCaP. Cells were cultured in phenol red-free RPMI-1640 supplemented with 10% charcoal-stripped fetal bovine serum, with concentrations of dihydrotestosterone (DHT) ranging from 0-10(-7) M, in a 4-day culture system. A bell-shaped growth response was reproduced with a peak level of cell count at 10(-10) M DHT. PSA secretion from these cells did not increase significantly until the DHT level in the medium reached 10(-9) M. A progressive increase in PSA secretion was observed at higher DHT concentrations accompanied with a progressive decline in cellular proliferation. The results of immunocytochemical analysis of PSA localization indicated that the proportion of cells with positive staining for PSA also increased with increasing concentrations of DHT. Analysis of androgen receptors, as determined by both immunocytochemistry and Western blot analysis, showed a decline in nuclear androgen receptor at low concentrations of DHT and an increase in the amount of receptor protein at high concentrations. These results indicated that the androgen-induced bell-shaped growth response in LNCaP cells represented the manifestation of two different cellular events in dose-related manner: cellular proliferation at low DHT concentrations and increased production of PSA at high DHT concentrations.