Key promoter elements involved in transcriptional activation of the cancer-related gene coding for S100P calcium-binding protein

Abstract

S100P gene encodes a calcium-binding protein expressed in different tumor tissues and is functionally implicated in malignant phenotype. Despite consistent relationship to cancer, regulation of S100P gene expression has remained unexplored. Here we determined the transcription start and defined the S100P core promoter. Using a series of the promoter constructs analyzed by dual luciferase reporter assay, we identified SMAD, STAT/CREB and SP/KLF binding sites as critical cis-elements required for S100P expression in cancer cells. We also demonstrated in EMSA that these elements bind nuclear factors, and showed their functional significance by promoter deletion analysis. This study represents the first coherent contribution to understanding of factors and pathways responsible for S100P gene activation in cancer.