Weng Jinsheng, Ma Wenbin, Mitchell Dianne, Zhang Jianshe, Liu Mingyao
Alkek Institute of Biosciences and Technology, Department of Medical Biochemistry and Genetics, Texas A&M University System Health Science Center, 2121 W. Holcombe Blvd., Houston, Texas 77030, USA.
J Cell Biochem. 2005 Dec 1;96(5):1034-48. doi: 10.1002/jcb.20600.
PSGR is a newly identified human prostate tissue-specific gene belonging to the G-protein coupled receptor (GPCR) family. Overexpression of PSGR is associated with human prostate intraepithelial neoplasia (PIN) and prostate tumors, suggesting PSGR may play an important role in early prostate cancer development and progression. To understand the regulation of tissue-specific expression of human PSGR and its upregulation mechanism in prostate cancers, we characterized the promoter region of PSGR and analyzed the control mechanism for PSGR expression in human prostate tissues/cells. In this report, we demonstrate that two distinct promoters control the transcriptional regulation of PSGR in human prostate cells. The first promoter region includes exon 1 and a TATA box at -31 site. The minimal DNA sequence with promoter activity is about 123 bp upstream of exon 1. Exon 1 contains tissue specific regulatory activity for the first promoter of PSGR gene. The second promoter is located in the upstream region of exon 2, which is a TATA-less and non-GC-rich promoter. Primer extension and RNA protection assays (RPA) revealed that the transcription driven by the second promoter is initiated at the junction of intron and exon 2 within a cluster of nucleotides located about 250 bp upstream from the junction. Both promoters show prostate cell-specific characteristics in our luciferase assays in transfected cells. Furthermore, we investigated the regulation of the promoter activities of the PSGR gene by different growth factors and cytokines, and demonstrated that interleukin-6 (IL-6) activates the promoter activities of PSGR in human prostate cancer cells. These data suggest that two functional promoters regulate the transcriptional expression of PSGR in human prostate tissues and PSGR is a new target for IL-6 transcriptional regulation.
PSGR是一种新发现的人类前列腺组织特异性基因，属于G蛋白偶联受体（GPCR）家族。PSGR的过表达与人类前列腺上皮内瘤变（PIN）和前列腺肿瘤相关，这表明PSGR可能在前列腺癌的早期发展和进展中发挥重要作用。为了了解人类PSGR组织特异性表达的调控及其在前列腺癌中的上调机制，我们对PSGR的启动子区域进行了表征，并分析了人类前列腺组织/细胞中PSGR表达的调控机制。在本报告中，我们证明了两个不同的启动子控制着人类前列腺细胞中PSGR的转录调控。第一个启动子区域包括外显子1和位于-31位点的TATA框。具有启动子活性的最小DNA序列位于外显子1上游约123 bp处。外显子1包含PSGR基因第一个启动子的组织特异性调控活性。第二个启动子位于外显子2的上游区域，它是一个无TATA且非富含GC的启动子。引物延伸和RNA保护分析（RPA）显示，由第二个启动子驱动的转录起始于位于内含子和外显子2交界处上游约250 bp处的一群核苷酸内。在转染细胞的荧光素酶分析中，两个启动子均显示出前列腺细胞特异性特征。此外，我们研究了不同生长因子和细胞因子对PSGR基因启动子活性的调控，并证明白细胞介素-6（IL-6）可激活人类前列腺癌细胞中PSGR的启动子活性。这些数据表明，两个功能性启动子调控人类前列腺组织中PSGR的转录表达，并且PSGR是IL-6转录调控的一个新靶点。
