Sucrase-isomaltase gene expression is inhibited by mutant hepatocyte nuclear factor (HNF)-1alpha and mutant HNF-1beta in Caco-2 cells.

Hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta are concerned in sucrase-isomaltase (SI) gene expression, and directly bind two sites (SIF2, SIF3) of the promoter of the SI gene. However, it is not completely clear that HNF-1alpha and HNF-1beta play a role in regulation of SI gene expression. To clarify mechanisms of SI gene expression regulated by HNF-1alpha and HNF-1beta, we established four stable cell lines based on enterocyte-like cell line Caco-2, in which wild HNF-1alpha or wild HNF-1beta, or else mutant HNF-1alphaT539fsdelC or mutant HNF-1betaR177X was overexpressed. In the HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, but not in the wild HNF-1alpha cells and wild HNF-1beta cells, SI gene expression and enzyme activity were significantly diminished compared with that in Caco-2 cells. Moreover, to clarify whether or not stable cell differentiation was influenced by overexpression of these transgenes, alkaline phosphatase (ALP) gene expression and enzyme activity were measured. There were no changes in ALP gene expression or enzyme activity in these cells. These observations suggest that mutant HNF-1alphaT539fsdelC and mutant HNF-1betaR177X inhibits SI gene at the transcriptional level, resulting in decreased SI enzyme activity in Caco-2 cells. We propose that both HNF-1alpha and HNF-1beta would contribute to constitutive expression of the SI gene in the differentiated state in Caco-2 cells.