Prostate cancer cell type-specific regulation of the human PTHrP gene via a negative VDRE.
Prostate cancer cell type-specific regulation of the human PTHrP gene via a negative VDRE.
复制标题
通过负 VDRE 对人类 PTHrP 基因进行前列腺癌细胞类型特异性调节。
DOI：
10.1016/s0303-7207(03)00148-5
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发表时间：
2003
影响因子：
4.1
通讯作者：
Falzon,Miriam
中科院分区：
文献类型：
--
作者：
TovarSepulveda,VeronicaA;Falzon,Miriam
甲状旁腺激素相关蛋白(PTHrP)由前列腺癌细胞表达。由于PTHrP促进了前列腺癌细胞的生长并增强了其溶骨作用，因此控制PTHrP在这些细胞中的表达水平是很重要的。我们发现，1，25-二羟基维生素D3(1，25(OH)2D3)及其非钙化类似物EB1089能抑制人前列腺癌PC-3和LNCaP细胞中PTHrP的mRNA和蛋白水平。人甲状旁腺素rP基因含有与甲状旁腺激素基因中的维生素D阴性反应元件同源的序列元件。该DNA序列(NVDREhPTHrP)与PC-3和LNCaP细胞核提取液中存在的维生素D受体(VDR)结合。然而，当克隆SV40启动子的上游并瞬时转染PC-3和LNCaP细胞时，nVDREhPTHrP下调LNCaP细胞对1，25(OH)2D3或EB1089处理的启动子活性，而不是PC-3细胞。这些结果可能有助于解释为什么一些前列腺癌似乎对维生素D类似物的治疗无效。
Parathyroid hormone-related protein (PTHrP) is expressed by prostate cancer cells. Since PTHrP increases the growth and enhances the osteolytic effects of prostate cancer cells, it is important to control the level of PTHrP expression in these cells. We show that 1,25-dihydroxyvitamin D3(1,25(OH)2D3) and its non-calcemic analogue, EB1089, suppress PTHrP mRNA and protein levels in the human prostate cancer cell lines PC-3 and LNCaP. The human PTHrP gene contains a sequence element homologous to the negative vitamin D response element within the parathyroid hormone gene. This DNA sequence (nVDREhPTHrP) bound the vitamin D receptor (VDR) present in nuclear extracts from both PC-3 and LNCaP cells. However, when cloned upstream of the SV40 promoter and transiently transfected into PC-3 and LNCaP cells, nVDREhPTHrPdownregulated promoter activity in response to 1,25(OH)2D3or EB1089 treatment in LNCaP, but not in PC-3, cells. These results may help to explain why some prostate cancers appear to be refractory to treatment with vitamin D analogues.