Sucrasc-Isomaltase Gene Expression Is Inhibited by Mutant Hepatocyte Nuclear Factor (HNF)-1α and Mutant HNF-1β in Caco-2 Cells

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Hepatocyte nuclear factor (HNF)-1α and HNF-1β are concerned in sucraseisomaltase (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-1α and HNF-1β play a role in regulation of SI gene expression. To clarify mechanisms of SI gene expression regulated by HNF-1α and HNF-1β, we established four stable cell lines based on enterocyte-like cell line Caco-2, in which wild HNF-1α or wild HNF-1β, or else mutant HNF-1αT539fsdelC or mutant HNF-1βR177X was overexpressed. In the HNF-1αT539fsdelC cells and HNF-1βR177X cells, but not in the wild HNF-1α cells and wild HNF-1β 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-1αT539fsdelC and mutant HNF-1βR177X inhibits SI gene at the transcriptional level, resulting in decreased SI enzyme activity in Caco-2 cells. We propose that both HNF-1α and HNF-1β would contribute to constitutive expression of the SI gene in the differentiated state in Caco-2 cells.
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