The Caudal-related homeodomain protein CDX1 activates proliferating cell nuclear antigen expression in hepatocellular and colorectal carcinoma cells

Abstract

Cdx1 and Cdx2 are known as Caudal-related homeodomain transcription factors important in the early differentiation and maintenance of intestinal epithelial cells. Cdx1 and Cdx2 are expressed in the small intestine and colon of fetus and adult. Most previous studies suggested that Cdx2 inhibits proliferation. Several target genes of Cdx2 have been identified. However, the effect of Cdx1 on cell proliferation is currently controversial and its target genes except for Hox-A7 remain unknown. In this study, we found several potential Caudal-related homeodomain binding sequences in the 5'-flanking region of human PCNA gene. Cotransfection experiments, using human PCNA reporter plasmid and CDX1 and CDX2 expression plasmids, showed that CDX1 transactivates human PCNA gene promoter activity in hepatocellular cell line (HepG2) and colorectal carcinoma cell lines (Colo320HSR and HCT116), while CDX2 does not. CDX1-induced PCNA expression was also detected in immunoblot and cytochemistry experiments. In BrdU incorporation experiments, CDX1 enhanced the incorporated BrdU. Taken together, our results suggest that CDX1 have a pro-proliferative effect on proliferation through transactivation of PCNA promoter activity.