Identification and characterization of the human SLC5A8 gene promoter

Abstract

The human SLC5A8 gene is a tumor suppressor. Its silencing may contribute to the carcinogenesis and progression of various tumors, which makes this gene an attractive molecular marker and a potential target for diagnosis and therapy. Little is known about transcriptional mechanisms controlling SLC5A8 gene expression. To better understand the molecular mechanisms regulating SLC5A8 expression, we characterized the 5'-regulatory region and a part of exon 1. Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPbeta) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPbeta and Sp1 transcription factors might have functions in SLC5A8 transcription. Taken together, our results elucidate the mechanism underlying the regulation of SLC5A8 gene transcription and also define a novel regulatory sequence that may be used to increase expression of the SLC5A8 gene in cancer gene therapy.