HIF-1alpha cDNAs were RT-PCR amplified from three prostate cancer cell lines (LNCaP, PC-3, and DU145), from five different human hormone-resistant prostate cancers and one normal prostate, all microdissected, and were sequenced to determine whether the HIF-1alpha gene products were wildtype or mutant.
Here, we show that treatment of prostate cancer PC-3 and LNCaP cells with the benzoquinone ansamycin geldanamycin, an Hsp90-specific inhibitor, induced degradation of HIF-1alpha protein in a dose- and time-dependent manner under both normoxia and hypoxia.
Identification of hypoxia-inducible factor-1alpha (HIF-1alpha) polymorphism as a mutation in prostate cancer that prevents normoxia-induced degradation.
These results show that over-expression of HIF-1alpha directly stimulates the invasive potency of human prostate carcinomaLNCaP cells through the matrix gel.
The importance of HIF-1alpha in tumor progression makes it a logical target for chemoprevention strategies in patients at higher genetic risk of breast and prostate cancer with Cox 2 inhibitors or 2-methoxyestradiol, as well as a target for new approaches to inhibiting angiogenesis.
These data provide evidence for the important role of GA in inhibition of angiogenesis and also invasion mediated by HIF-1alpha in prostate cancer cells.
HIF-1 may be involved in prostate cancer as well as the AR, but the involvement of HIF-1 in prostate cancer angiogenesis and progression has not been fully elucidated.
In this study, we investigated the effects of chrysin on expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor in human prostate cancer DU145 cells.
To determine its potential role as a marker for prostate cancer (CaP) diagnosis, HIF-1alpha mRNA levels were measured in blood samples of patients diagnosed with different stages of prostatic disease.
Potentially functional single nucleotide polymorphisms (SNP) in genes important in prostate angiogenesis (VEGF, HIF1A, and NOS3) have previously been associated with risk or severity of prostate cancer.
Here we report that ROS induced by a direct application of H(2)O(2) and menadione to DU145 human prostate carcinoma resulted in accumulation of HIF-1alpha protein by attenuation of its degradation and activation of its transcriptional activity in an AMPK-dependent manner.
Moreover, HIF-1 alpha protein increase during serum deprivation correlated with increased cell survival, while suppression of HIF-1 alpha expression significantly decreased PCa cell viability.
Inhibition of HIF-1 alpha and VEGF expression by the chemopreventive bioflavonoid apigenin is accompanied by Akt inhibition in human prostate carcinoma PC3-M cells.
These studies highlight the importance for the Egr1 transcription factor in the hypoxic response in cultured prostate cancer cell lines, and indicate that the response of Egr1 is upstream of HIF-1 in these cells.
This study provides the first evidence of an increased risk for clinically localised prostate cancer in men carrying the C1772THIF-1alpha gene polymorphism.
We previously reported that normoxic, serum-deprived prostate cancer (PCa) cells upregulate hypoxia-inducible factor-1alpha (HIF-1alpha) protein, which promotes survival during serum deprivation via insulin-like growth factor-2 (IGF-2) upregulation.
HIF-1alpha-dependent BCL-xL overexpression may be an important mechanism by which HIF-1alpha protects prostate cancer cells from apoptosis and leads to treatment resistance.