Because TCF4 (TCF7L2) is one of the major Wnt/β-catenin signaling-associated transcription factors and binds to Irs1 promotor in the rat hepatoma cell line H4IIE16, 21, the effect of dominant-negative TCF4 cDNA (DN-TCF4) on the regulation of Irs1 in primary hepatocytes was examined. This evidence concerns the gene TCF7L2 and hepatocellular carcinoma.