This review presents a synopsis of the genes induced by hypoxia in the context of breast cancer and discusses how upregulation of HIF-1 activity, and the homologous factor HIF-2, are not only fundamental for the adaptation to hypoxia but also may be critical for tumor progression.
Previous studies showed that concentrations of its subunit HIF-1alpha, as a surrogate for HIF-1 activity, are increased during breast carcinogenesis and can independently predict prognosis in breast cancer.
The inhibitory activity of 103D5R against HIF-1alpha was clearly shown under normoxia and hypoxia in cells derived from different cancer types, including glioma, prostate, and breast cancers.
HIF-1alpha has emerged as an important transcription factor in breast cancer and prostate cancer biology, and is expressed in the early stages of mammary and prostate carcinogenesis.
Since both HIF-1alpha and ER are highly active in the ER-positive breast cancer, C Delta553 has the potential to be developed as a protein drug to treat breast cancer by blocking these two signaling pathways.
In this review we will summarise the role of hypoxia in breast cancer and specifically outline the importance of hypoxia and HIF-1alpha regarding prognostic and treatment-specific implications.(Part of a Multi-author Review).
HIF-1alpha overexpression was significantly more frequent in BRCA1 related breast cancers (27/30, 90%) than in sporadic controls (88/200, 44%) (P < 0.0001).
We show that hsa-miR-210 overexpression is induced by hypoxia in a HIF-1alpha- and VHL-dependent fashion and its expression levels in breast cancer samples are an independent prognostic factor.
In our study, we investigated whether polymorphisms of the HIF-1alpha gene may account for the expression patterns of HIF-1alpha protein and impact of clinical progression in breast cancer.
Here we show that HIF-1alpha protein significantly accumulated in human breast cancer MDA-MB-231 cells in response to the pro-inflammatory cytokine IL-1beta, but not in COX-2-silenced MDA-MB-231 cells.
We found that TNFalpha enhances HIF-1alpha protein expression in various breast cancer cell lines under either normoxic or hypoxia-mimicking conditions, but has little effect on the HIF-1alpha mRNA level.
Our meta-analysis suggests that the HIF-1alpha1772 C/T polymorphism is significantly associated with higher cancer risk, and 1790 G/A polymorphism is significantly associated with decreased breast cancer risk.