The zinc-finger transcription factor Snail downregulates proliferating cell nuclear antigen expression in colorectal carcinoma cells

Abstract

The Snail family of zinc-finger protein is a transcription repressor that is involved in the development of vertebrate and invertebrate embryos as well as in tumor progression. This family leads to broad biological functions such as cell differentiation, cell motility, cell cycle regulation and apoptosis. However, the target genes of Snail remain little known. In this study, we found several potential Snail binding sequences in the 5'-flanking region of human PCNA gene. Cotransfection experiments showed that Snail reduces human PCNA gene promoter activity in colorectal carcinoma cell lines, HCT116 and Colo320HSR. Snail-reduced PCNA expression was detected in immunoblotting and immunochemistry. In BrdU incorporation experiment, Snail inhibited the BrdU incorporation. Electrophoretic mobility shift assays showed that Snail can bind to the potential Snail recognition sites in the human PCNA promoter. Taken together, our results suggest that Snail may have an inhibitory effect on cell proliferation through down-regulation of PCNA expression as a novel target.