Characterization of human STAMP2 promoter and 5' flanking sequence

Abstract

Prostate cancer is the most common non-skin cancer and the third leading cause of cancer death in men in developed countries. No effective cure has yet been found to treat the hormone refractory state of PCa. In addition to study the actions of the AR, a focus has been directed towards identifying androgen-regulated genes as potential biomarkers and therapeutic targets for the disease. hSTAMP2 is one of these genes identified in our laboratory when searching for genes differentially expressed in the early stages of prostate cancer. Our previous studies have shown that its mRNA is highly expressed in the prostate tissue and upregulated in prostate tumor samples. Moreover, its overexpression increased colony formation and cell growth of PCa cell lines, suggesting a possible function in prostate pathology. Furthermore, its mRNA expression appeared to be androgen stimulated. These results suggest a possible androgen –dependent cis-regulatory elements located in the hSTAMP2 5’flanking sequence. Computational analyses reveal a number of transcription factor binding sites and androgen response elements (AREs) that may be of importance for the hSTAMP2 gene regulation. Reporter gene assays show the different effect that androgen has on the hSTAMP2 putative promoter activity in two different PCa cell lines. The complexity of the androgen regulation of hSTAMP2 expression is supported in experiments where LNCaP cells were treated with CHX, suggesting the requirement of de novo protein synthesis for the AR mediated hSTAMP2 gene regulation. Additional studies are needed to identify potential AREs located in the sequences further upstream and downstream of the hSTAMP2 gene.