Because fibrous remodeling of the subepithelium could limit delivery of nutrients and oxygen to the epithelium, we assessed expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CA IX) as markers of cellular hypoxia.
Taken together, our results suggest that besides the PI3K pathway, the MAPK cascade is involved in the regulation of CA9 gene expression under both hypoxia and high cell density.
In contrast, coexpression of HIF-1alpha and CAIX in the epithelium in phyllodes tumors points to epithelial hypoxia, most probably caused by relatively distant blood vessels.
Our findings suggest that hypoxia regulates both expression and activity of CA IX in order to enhance the extracellular acidification, which may have important implications for tumor progression.
The SP1/SP3 and hypoxia-response element in the CA9 promoter thus may represent a novel type of enhancer capable of mounting responses to a wider range of hypoxic conditions.
Mechanisms underlying erythrocyte and endothelial nitrite reduction to nitric oxide in hypoxia: role for xanthine oxidoreductase and endothelial nitric oxide synthase.
1.The aim of the present study was to investigate whether pre-eclampisa, a state of placental hypoxia, is associated with placental abnormalities in the amount, distribution and expression of endothelial nitric oxide synthase (eNOS).2.
Also, introduction of an antisense oligonucleotide for Egr-1 diminishes EGFR expression during hypoxia, indicating that the up-regulation of EGFR by hypoxia is mediated through Egr-1.
Thus, in progressive but not in stable proteinuric kidney disease, human PTECs show an attenuated VEGF-A expression despite an activation of intracellular hypoxia response and VEGF signaling pathways, which might be due to a reduced expression of positive coregulators, such as EGF and IGF-1.
These data suggest that hypoxia enhances the expression of MUC1 through the transcriptional regulation by HIF-1alpha in a human lung epithelial cell line.
Chromatin immunoprecipitation identified a previously unappreciated binding site for the hypoxia inducible factor-1 (HIF-1), and promoter studies established its relevance by loss of repression following point mutation.
We suggest a dual role for HIF-1alpha in providing a survival or death signal, based on hypoxia duration, and consider the nuclear transcription factor, CREB, to be a possible target for hypoxic therapy against leukemia disease.
Here we report an RNA switch in human vascular endothelial growth factor-A (VEGFA, also known as VEGF) mRNA 3' untranslated region (UTR) that integrates signals from interferon (IFN)-gamma and hypoxia to regulate VEGFA translation in myeloid cells.
Thioredoxin-interacting protein, a putative tumor suppressor gene, is induced in response to hypoxia in a HIF-1alpha-dependent manner in pancreatic cancer cells, resulting in increased apoptosis and increased sensitivity to platinum anticancer therapy.
Here, we provide the first evidence that sphingosine kinase 1 (SphK1), an oncogenic lipid kinase balancing the intracellular level of key signaling sphingolipids, modulates the transcription factor hypoxia inducible factor 1alpha (HIF-1alpha), master regulator of hypoxia.