Regulation of human prostate-specific G-protein coupled receptor, PSGR, by two distinct promoters and growth factors

Abstract

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.