doi:10.1038/nindia.2011.145 Published online 11 October 2011
Researchers have shown that one form of the female sexual hormone estrogen stimulates breast cancer cells to accumulate a crucial transcription factor, a finding that might have a role in fighting cancer. They suggest that further understanding of estrogen signaling could help identify a new drug target that can overcome resistance to hormonal replacement therapy and improve the survival rate of cancer patients.
The transcription factor HIF-1α has been shown to regulate many genes responsible for growth of new blood cells (angiogenesis), production of red blood cells (erythropoiesis), and glucose metabolism in many cancers. The researchers found that the most potent form of circulating estrogen – 17β-Estradiol (E2) – stimulates breast cancer cells to rapidly accumulate HIF-1α as well as HIF1 promoter activity through nongenomic signaling.
The female steroid hormone estrogen plays an important role in the development of breast cancer, a leading cause of cancer related deaths in women around the world. The role of estrogen in the development of breast cancer has been poorly understood.
Much of the research is focused on studying the transcriptional control of target genes via binding of its receptor to consensus genomic sequence. Despite its classical mode of action, evidence has emerged that estrogen could regulate intracellular signaling by interacting with non-receptor tyrosine kinase c-Src, p85 subunit of PI3K and MAPK pathways.
The researchers showed that estrogen induced HIF-1α expression involves enhanced HIF-1α translation mediated by c-Src and mTOR signaling. The regulation of HIF-1α by estrogen can explain, in part, how estrogen signaling leads to breast cancer progression, they say.