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.
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.
These results provide evidence of a key signalling pathway involving HIF-1alpha and TWIST that promotes metastasis in response to intratumoural hypoxia.
Chromatin immunoprecipitation assay demonstrated that HIF-1 alpha directly bound to this region under normoxia, and this binding activity was significantly enhanced under hypoxia.
These results suggest that the hypoxia induces the migration of CASMCs, and that the migration is elicited by TSP-1 of which induction is fully dependent on the stabilization of HIF-1alpha, in autocrine regulation.
In conclusion, PCAF regulates the balance between cell-cycle arrest and apoptosis in hypoxia by modulating the activity and protein stability of both p53 and HIF-1alpha.
Alltogether, our data indicate that HIF-1alpha and hypoxia play a crucial role for DC activation in inflammatory states, which is highly dependent on glycolysis even in the presence of oxygen.
In conclusion, the signals evoked by hypoxia and after EDHB treatment differentially regulate HO-1 mRNA expression through HIF-1alpha-independent mechanisms.
Thus, hypoxia dictates an anti-inflammatory program by driving expression of HIF-1alpha that acts to increase the number and suppressive properties of naturally occurring CD4(+)CD25(+) Treg.
These findings indicate that HIF-1alpha is elevated in both TM and GBM, suggesting that although hypoxia is one of the most important and powerful stimuli for HIF-1alpha elevation and consequently angiogenesis, other mechanisms may play roles in HIF-1alpha stimulation in benign brain tumors such as TM.
Our studies show that PlGF-induced expression of the potent vasoconstrictor ET-1 and its cognate ET-BR receptor occur via activation of HIF-1 alpha, independent of hypoxia.