Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter
Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter
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DOI：
10.1074/jbc.271.11.6379
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发表时间：
1996-03-15
影响因子：
4.8
通讯作者：
Trapman, J
中科院分区：
文献类型：
--
作者：
Cleutjens, KBJM;vanEekelen, CCEM;Trapman, J
前列腺特异性抗原（PSA）基因的转录受雄激素调节，PSA启动子在-170位包含序列AGAACAgcaAGTGCT，该序列与ARE（雄激素反应元件）共有序列GGTACAnnnTGTTCT密切相关。该序列是高亲和力雄激素受体 (AR) 结合位点，在转染的 LNCaP 细胞中充当功能性 ARE。起始于 -400 的 35 个碱基对片段（ARR：雄激素反应区；GTGGTGCAGGGATCAGGGAGTCTCACAATCTCCTG）与 ARE 配合进行 PSA 启动子的雄激素诱导。具有三个 ARR 拷贝与最小 PSA 启动子连接的构建体显示出强大的（104 倍）雄激素诱导活性。 ARR 还能够赋予雄激素对最小胸苷激酶启动子的反应性。 AR 结合和转录活性均位于 20 碱基对的 ARR 亚片段：CAGGGATCAGGGAGTCTCAC (2S) 中，突变分析表明 2S 片段中的序列 GGATCAgggAGTCTC 是功能活性、低亲和力的 AR 结合位点。与 AR 一样，糖皮质激素受体能够刺激 PSA 启动子活性。 ARE 和 ARR 艺术：参与 PSA 启动子的地塞米松调节，LNCaP 细胞中 AR 和糖皮质激素受体对 ARR-PSA 和 ARR-胸苷激酶启动子构建体的活性比其他细胞类型（COS、HeLa、Hep3B 和 T47D 细胞）高 20-100 倍，表明（前列腺）细胞特异性。
Transcription of the prostate-specific antigen (PSA) gene is androgen regulated, The PSA promoter contains at position -170 the sequence AGAACAgcaAGTGCT, which is closely related to the ARE (androgen response element) consensus sequence GGTACAnnnTGTTCT. This sequence is a high affinity androgen receptor (AR) binding site and acts as a functional ARE in transfected LNCaP cells. A 35-base pair segment starting at -400 (ARR: androgen response region; GTGGTGCAGGGATCAGGGAGTCTCACAATCTCCTG) cooperates with the ARE in androgen induction of the PSA promoter. A construct with three ARR copies linked to a minimal PSA promoter showed a strong (104-fold) androgen induced activity. The ARR was also able to confer androgen responsiveness to a minimal thymidine kinase promoter. Both AR binding and transcriptional activity resided in a 20-base pair ARR subfragment: CAGGGATCAGGGAGTCTCAC (2S), Mutational analysis indicated that the sequence GGATCAgggAGTCTC in the 2S fragment is a functionally active, low affinity AR binding site. Like AR, the glucocorticoid receptor was able to stimulate PSA promoter activity. Both the ARE and ARR art: involved in dexamethasone regulation of the PSA promoter, Both the AR and glucocorticoid receptor were 20-100 fold more active on ARR-PSA and ARR-thymidine kinase promoter constructs in LNCaP cells than in other cell types (COS, HeLa, Hep3B, and T47D cells), indicating (prostate) cell specificity.