Androgen regulation of the cell-cell adhesion molecule-1 (Ceacam1) gene.
Androgen regulation of the cell-cell adhesion molecule-1 (Ceacam1) gene.
复制标题
雄激素对细胞间粘附分子 1 (Ceacam1) 基因的调节。
DOI：
10.1016/s0303-7207(01)00638-4
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发表时间：
2001
影响因子：
4.1
通讯作者：
Lin,SH
中科院分区：
文献类型：
--
作者：
Phan,D;Sui,X;Chen,DT;Najjar,SM;Jenster,G;Lin,SH
先前的研究已经证实，细胞-细胞粘附分子-1（CEACAM1，以前称为 C-CAM1）在前列腺癌中发挥肿瘤抑制因子的作用，并参与前列腺生长和分化的调节。然而，调节前列腺中 CEACAM1 表达的分子机制尚不清楚。由于前列腺上皮细胞的生长受雄激素调节，我们研究了雄激素和雄激素受体 (AR) 对 CEACAM1 表达的影响。瞬时转染实验表明，AR 可以以配体依赖性方式增强 Ceacam1 启动子活性，并且调控元件位于 Ceacam1 基因 5' 侧翼区域相对较短（-249 至 -194 bp）的片段内。这种雄激素调节可能是通过直接 AR 启动子结合来实现的，因为 DNA 结合缺陷的突变 AR 无法上调报告基因表达。此外，电泳迁移率变动分析表明 AR 与该序列特异性结合，并且潜在 ARE 序列的突变分析揭示了该序列中 AR 激活 Ceacam1 基因所需的区域。因此，雄激素对Ceacam1基因表达的调节可能是雄激素调节前列腺功能的机制之一。
Previous studies have established that the cell–cell adhesion molecule-1 (CEACAM1, previously known as C-CAM1) functions as a tumor suppressor in prostate cancer and is involved in the regulation of prostate growth and differentiation. However, the molecular mechanism that modulates CEACAM1 expression in the prostate is not well defined. Since the growth of prostate epithelial cells is androgen-regulated, we investigated the effects of androgen and the androgen receptor (AR) on CEACAM1 expression. Transient transfection experiments showed that the AR can enhance the Ceacam1 promoter activity in a ligand-dependent manner and that the regulatory element resides within a relatively short (−249 to −194 bp) segment of the 5′-flanking region of the Ceacam1 gene. This androgen regulation is likely through direct AR-promoter binding because a mutant AR defective in DNA binding failed to upregulate reporter gene expression. Furthermore, electrophoretic mobility shift assays demonstrated that the AR specifically binds to this sequence, and mutation analysis of the potential ARE sequences revealed a region within the sequence that was required for the AR to activate the Ceacam1 gene. Therefore, the regulation of Ceacam1 gene expression by androgen may be one of the mechanisms by which androgen regulates prostatic function.