GROWTH OF LNCAP HUMAN PROSTATE-CANCER CELLS IS STIMULATED BY ESTRADIOL VIA ITS OWN RECEPTOR
GROWTH OF LNCAP HUMAN PROSTATE-CANCER CELLS IS STIMULATED BY ESTRADIOL VIA ITS OWN RECEPTOR
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DOI：
10.1210/en.136.5.2309
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发表时间：
1995-05-01
期刊：
影响因子：
4.8
通讯作者：
CARRUBA, G
中科院分区：
文献类型：
--
作者：
CASTAGNETTA, LA;MICELI, MD;CARRUBA, G
我们报告说，生理雌二醇 (E(2)) 浓度显着刺激了 LNCaP 人类前列腺癌细胞的生长（比对照高出 120%）。正如其他人报道的那样，这种生长增加似乎与睾酮或二氢睾酮诱导的生长增加相当。本文为 LNCaP 细胞中雌激素结合蛋白和信使 RNA 转录本提供了新的说明性证据。事实上，1) 逆转录酶-聚合酶链式反应系统记录了雌激素受体 (ER) 的正常信使 RNA； 2) 放射性配体结合测定可以检测可溶细胞和核细胞部分中高亲和力、降低容量的结合位点； 3) 免疫细胞化学分析显示 ER 和孕酮受体的染色一致强烈。与其他人类雌激素反应性乳腺癌细胞 MCF7 和 ZR75-1 相比，LNCaP 细胞中的 ER 表达并未显着降低，如 ER 转录本水平、每个细胞的位点数量或每 mg DNA 的飞摩尔数以及免疫细胞化学染色的百分比和强度所示。通过将 LNCaP 与另一种人类前列腺癌细胞系 PC3 匹配获得的 ER 表达的相对估计值，在 LNCaP 细胞中始终显示出显着且一致的较高水平。在 LNCaP 细胞的任一细胞区室中检测到相对较高的 I 型 ER 含量，同时对孕酮受体进行高强度染色。此外，有证据表明，合成雄激素 R1881 不会竞争 E(2) 的 I 型结合，并且纯抗雌激素 ICI-182,780 可以完全逆转任何 E(2) 诱导的生长，但不受抗雄激素 Casodex 的影响，这清楚地表明 LNCaP 细胞对 E(2) 的生物反应是通过其自身受体介导的。
We report that growth of LNCaP human prostate cancer cells is significantly stimulated (up to 120% above control) by physiological estradiol (E(2)) concentrations. This growth increase appears to be comparable to that induced by either testosterone or dihydrotestosterone, as also reported by others. This paper presents novel illustrative evidence for estrogen-binding proteins and messenger RNA transcripts in LNCaP cells. In fact, 1) the reverse transcriptase-polymerase chain reaction system documented normal messenger RNA for estrogen receptors (ER); 2) the radioligand binding assay allowed the detection of high affinity, reduced capacity binding sites in both soluble and nuclear cell fractions; and 3) the immunocytochemical analysis showed a consistently intensive staining for both ER and progesterone receptors. Compared to other human estrogen-responsive mammary cancer cells, MCF7 and ZR75-1, ER expression in LNCaP cells was not significantly lower, as shown by levels of the ER transcripts, number of sites per cell, or femtomoles per mg DNA as well as the percentage and intensity of immunocytochemical staining. A relative estimate of ER expression obtained by matching LNCaP with another human prostate cancer cell line, PC3, always displayed significantly and consistently higher levels in LNCaP cells. The detection of relatively high type I ER content in either cell compartment of LNCaP cells was paralleled by a highly intensive staining for progesterone receptors. In addition, evidence that the synthetic androgen R1881 did not compete for type I binding of E(2) and that any E(2)-induced growth was completely reversed by the pure antiestrogen ICI-182,780, but unaffected by the antiandrogen Casodex, clearly suggests that the biological response of LNCaP cells to E(2) is mediated via its own receptor.