前列腺组织与LNCaP细胞的雄激素受体亚型研究

目的 :研究雄激素受体 (AR)亚型在人前列腺良性增生与前列腺癌组织以及LNCaP细胞系中的表达 ,探讨AR亚型表达组织之间的差异。　方法 :应用氚标技术与聚丙烯酰胺凝胶等电聚焦电泳的方法 ,对相应组织的AR亚型进行分析。　结果 :4 1例AR阳性的前列腺增生组织、3例前列腺癌组织和LNCaP细胞中 ,发现有 3个AR亚型的表达 ,其等电点 (pI)分别在6 .5、6 .0和 5 .3。在前列腺增生标本中 ,15例 (36 .5 % )表达 pI6 .5、6 .0、5 .3亚型 ,10例 (2 4 .4 % )表达 pI6 .5、5 .3亚型 ,5例 (12 .2 % )表达 pI6 .5、6 .0亚型 ,4例 (9.8% )表达 pI6 .0、5 .3亚型 ,2例(4.9% )表达 pI6 .5亚型 ,2例 (4.9% )表达 pI6 .0亚型 ,3例 (7.3% )表达 pI5 .3亚型。在 3例前列腺癌组织中 ,1例表达pI 6 .5、6 .0、5 .3亚型 ,1例表达pI 6 .5、6 .0亚型 ,1例 3种亚型均不表达。LNCaP细胞表达pI 6 .5、6 .0、5 .3亚型。氚标的双氢睾酮 (DHT)与 3种受体亚型的结合 ,可以被非氚标的DHT、睾酮 (T)竞争抑制 ,而孕酮、雌二醇和己烯雌酚对此却无竞争抑制作用。　结论 :AR亚型的表达 ,在不同的病人与疾病和LNCaP前列腺癌细胞系之间存在差异 ,提示不同病人对前列腺癌的内分泌疗法有不同的反应性

Androgen Receptor Isoforms in LNCaP Cell and Human Prostate

Objectives: To investigate the androgen receptor (AR) isoforms expression in human benign and malignant prostatic tissues and LNCaP cells. Methods: Using high resolution isoelectric focusing (IEF), the different expression of AR isoforms were demonstrated in human benign and malignant prostatic tissues and LNCaP cells. Results: Data were obtained from 41 AR positive BPH, three prostatic cancer specimens, and LNCaP cells. From these materials, three types of AR isoforms were detected with pI values at 6.5,6.0 and 5.3. In the case of BPH tissues, 15 (36.5%) specimens expressed all the three types of isofoms at pI 6.5 , 6.0 and 5.3 , and 10 (24.4%) samples contained isoforms at pI 6.5 and 5.3, five (12.2%) samples indicated isoforms at pI 6.5 and 6.0 , four ( 9.8 %) showed the isoforms at pI 6.0 and 5.3. Of all the 41 specimens, two (4.9%) and two (4.9%) as well as three ( 7.3 %) denoted the isoforme at pI 6.5,6.0 and 5.3 respectively. As for three prostatic cancer specimens, one sample showed all the three types of AR isoforms at pI 6.5,6.0,5.3, but another specimen expressed at pI 6.5 and 6.0, and only one failed to indicate any types of isoforms. LNCaP cells expressed all three types of AR isoforms at pI 6.5,6.0 and 5.3. Binding of 3 H dihydrotestosterone to these three types of isoforms was inhibited by the addition of 100 fold excess of DHT and testosterone. No effect of progesterone, oestradiol and diethylstilboestrol on tritiated hormone binding was observed. Conclusions: The expression of AR isofoms is different among various patients and different between BPH and LNCaP cells, though no clear explanation could be induced for this. These results suggest the possibility of explaining effective hormonal therapy to prostatic diseases in the future.