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Carbonic anhydrase IX (CAIX) is a hypoxia-regulated gene. It is over expressed   in a variety of cancers, including hepatocellular cancer. Transforming growth   factor β (TGFβ) is considered to have an impact on cancer biology due to its   important roles in cell proliferation and differentiation. The effect of the   TGFβ on CAIX expression under hypoxia and the mechanism underlying the role   of the hypoxia response element (HRE) on this expression are unknown. In this   study, we demonstrate that TGFβ upregulates CAIX expression under hypoxic   conditions in the Hep3B hepatoma cell line, indicating that the   mitogen-activated protein kinase (MAPK)- and   phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-signaling pathways   might be responsible for this response. Site-directed mutagenesis of the HRE   region in CAIX promoter reduced the TGFβ-induced CAIX promoter activity,   pointing to the significance of HRE for this response. Up regulation of   TGFβ-stimulated CAIX expression was consistent with the up regulation of   promoter activity of five different truncated constructs of the CAIX promoter   under hypoxia. Our findings show that the HRE region is critical for   TGFβ-induced CAIX expression, which is mainly controlled by MAPK and PI3K   pathways

The role of hypoxia response element in TGFβ-induced carbonic anhydrase IX expression in Hep3B human hepatoma cells