Mitchell S H, Murtha P E, Zhang S, Zhu W, Young C Y
Department of Urology, Mayo Graduate School, Mayo Foundation, 200 first Street SW, Guggenheim Building 1742B, Rochester, MN 55905, USA.
Mol Cell Endocrinol. 2000 Oct 25;168(1-2):89-99. doi: 10.1016/s0303-7207(00)00319-1.
Human glandular kallikrein (hK2) is an androgen regulated protein primarily expressed in the prostate and recently identified as a novel prostate cancer marker. A 5 kb 5' flanking region of the hK2 gene was isolated and sequenced to characterize the regulatory mechanisms for the expression of hK2 in the androgen responsive prostate cell line, LNCaP. Using gene transfer, gel shift, and mutagenesis assays we have identified an ARE in the 5' far upstream promoter region of the hK2 gene that is crucial for its regulation in LNCaP cells. This study further demonstrated that the hK2 upstream ARE plays a predominant role in androgenic response. More interestingly, previously identified AREs in the prostate specific antigen promoter and the hK2 proximal promoter exert little activity in LNCaP cells. This study for the first time identifies a unique ARE that alone mediates the function of the androgen receptor in LNCaP cells in a cell dependent manner. This study also examines the activity of this ARE with 1alpha, 25 dihydroxy-vitamin D3 on the expression of the hK2 gene in LNCaP cells.
人腺激肽释放酶（hK2）是一种雄激素调节蛋白，主要在前列腺中表达，最近被确定为一种新型前列腺癌标志物。分离并测序了hK2基因5kb的5'侧翼区域，以表征hK2在雄激素反应性前列腺细胞系LNCaP中表达的调控机制。通过基因转移、凝胶迁移和诱变分析，我们在hK2基因5'远上游启动子区域鉴定出一个雄激素反应元件（ARE），它对LNCaP细胞中的调控至关重要。这项研究进一步证明，hK2上游ARE在雄激素反应中起主要作用。更有趣的是，先前在前列腺特异性抗原启动子和hK2近端启动子中鉴定出的ARE在LNCaP细胞中几乎没有活性。这项研究首次鉴定出一个独特的ARE，它单独以细胞依赖的方式介导雄激素受体在LNCaP细胞中的功能。这项研究还检测了1α,25-二羟基维生素D3对该ARE在LNCaP细胞中hK2基因表达的活性。
