Hormonal regulation of H19 gene expression in prostate epithelial cells
Hormonal regulation of H19 gene expression in prostate epithelial cells
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DOI：
10.1677/joe.1.05696
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发表时间：
2004-10-01
影响因子：
4
通讯作者：
Curgy, JJ
中科院分区：
文献类型：
--
作者：
Berteaux, N;Lottin, S;Curgy, JJ
H19基因在mRNA样非编码RNA中转录。当考虑各种器官或细胞类型的肿瘤时，H19癌基因或肿瘤抑制剂状态仍然存在争议。为了解决通过雄激素类固醇激素（DHT：二氢睾丸激素）或肽激素（PRL：催乳素）对H19基因表达的潜在调节，我们在用化学介导者系统治疗的大鼠中进行了实验。这一体内实验范围表明，慢性高乳酸激素血症上皮细胞和基质细胞中的H19表达上调，而DHT下调了该基因。 PRL和DHT似乎是H19 RNA合成中的介体。我们研究了三种人前列腺上皮细胞系中的这些激素作用。在LNCAP癌细胞中，PRL和DHT的相反作用得到了证实。然而，在正常细胞（PNT1A）中，H19对胎牛血清（FCS）培养基中的激素不敏感，但在血清划分的培养基中反应迅速。在DU-145癌细胞系中测试了其雄激素独立性和攻击性，无论培养条件如何，激素对H19表达没有影响。最后，我们证明了PRL通过JAK2-STAT5转导途径上调LNCAP细胞中的H19表达。我们得出的结论是，H19表达受肽和雄性类固醇激素的调节。
The H19 gene is transcribed in an mRNA-like noncoding RNA. When tumors of various organs or cell types are considered, H19 oncogene or tumor-suppressor status remains controversial. To address the potential regulation of H19 gene expression by an androgen steroid hormone (DHT: dihydrotestosterone) or by a peptidic hormone (PRL: prolactin), we performed experiments in rats systemically treated with chemical mediators. This range of in vivo experiments demonstrated that chronic hyperprolactinemia upregulated the H19 expression in epithelial and stromal cells whereas DHT downregulated the gene. PRL and DHT appeared to be opposite mediators in the H19 RNA synthesis. We investigated these hormonal effects in three human prostate epithelial cell lines. In LNCaP cancer cells, the opposite effect of PRL and DHT was corroborated. However, in normal cells (PNT1A), H19 remained insensitive to the hormones in fetal calf serum (FCS) medium but became responsive in a serum-stripped medium. In the DU-145 cancer cell line, tested for its androgen-independence and aggressiveness, the hormones had no effect on H19 expression whatever the culture conditions. Finally, we demonstrated that PRL upregulated the H19 expression in LNCaP cells by the JAK2-STAT5 transduction pathway. We conclude that H19 expression is regulated by both a peptidic and a male steroid hormone.