Hormonal regulation of prostate-specific antigen messenger RNA in human prostatic adenocarcinoma cell line LNCaP.
Hormonal regulation of prostate-specific antigen messenger RNA in human prostatic adenocarcinoma cell line LNCaP.
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发表时间：
1991-07
期刊：
影响因子：
11.2
通讯作者：
Charles Y. F. Young;B. Montgomery;Paul E. Andrews;Shu-Dong Qiu;D. Bilhartz;D. Tindall
中科院分区：
文献类型：
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作者：
Charles Y. F. Young;B. Montgomery;Paul E. Andrews;Shu-Dong Qiu;D. Bilhartz;D. Tindall
前列腺特异性抗原（PSA）是kallikrein基因家族的一员，仅在人前列腺上皮细胞中表达。PSA蛋白已成为前列腺癌的重要生物学标志物。到目前为止，人们对前列腺细胞中PSA表达的调控知之甚少。在这项研究中，我们开发了一种特异性的寡核苷酸探针，它可以识别PSA，但不能识别人腺体的钾激肽。这是至关重要的，因为PSA和人腺体激肽肽在前列腺中表达水平相对较高，核苷酸序列同源性高（大于82%）。利用s标记的PSA特异性探针，PSA mRNA被定位在前列腺腺上皮内。Northern blot分析在LNCaP细胞（一种来源于人前列腺癌转移的细胞系）中检测到一个1.6千碱基的转录物。因此，我们利用LNCaP细胞研究雄激素对PSA mRNA表达的影响。一项时间过程研究表明，micbolerone（一种不可代谢的合成雄激素）可诱导PSA mRNA，并在9小时后达到最高水平。诱导PSA mRNA仅需0.3 nM的micbolerone。此外，天然雄激素二氢睾酮可诱导PSA mRNA表达，但合成糖皮质激素地塞米松或合成雌激素己烯雌酚不能诱导PSA mRNA表达。此外，在双氢睾酮存在的情况下，PSA mRNA被羟氟他胺（一种抗雄激素）抑制。这些结果强烈提示LNCaP细胞中雄激素对PSA mRNA的影响可能是通过雄激素受体的功能来实现的。
Prostate-specific antigen (PSA) is a member of the kallikrein gene family and is expressed exclusively in human prostatic epithelial cells. PSA protein has been an important biological marker for prostate cancers. Until now, very little was known about the regulation of PSA expression in prostatic cells. In this study, we have developed a specific oligonucleotide probe which recognizes PSA but not the human glandular kallikrein. This is crucial because both PSA and human glandular kallikrein are expressed in the prostate at relatively high levels and have high nucleotide sequence homology (greater than 82%). Utilizing a S-labeled PSA-specific probe, PSA mRNA was localized within the glandular epithelium of the prostate. Northern blot analysis detected a single 1.6-kilobase transcript in LNCaP cells, a cell line derived from a human prostate adenocarcinoma metastasis. Therefore, LNCaP cells were used to study the androgenic effects on PSA mRNA expression. A time course study demonstrated that PSA mRNA was induced by mibolerone (a nonmetabolizable synthetic androgen) and reached maximal levels after 9 h. The induction of PSA mRNA required as little as 0.3 nM mibolerone. In addition to mibolerone, PSA mRNA could be induced by the natural androgen, dihydrotestosterone, but not by the synthetic glucocorticoid, dexamethasone, or the synthetic estrogen, diethylstilbestrol. Moreover, in the presence of dihydrotestosterone, PSA mRNA was depressed by hydroxyflutamide (an antiandrogen). These results suggest strongly that the androgenic effects on PSA mRNA in LNCaP cells may be via the function of the androgen receptor.