ArticleBritish journal of cancer2011
Rapid non-genomic signalling by 17β-oestradiol through c-Src involves mTOR-dependent expression of HIF-1α in breast cancer cells.
Article in British journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Elevated aerobic glycolysis driven by p62-mTOR axis promotes arsenic-induced oncogenic phenotypes in human mammary epithelial cells.Archives of toxicology · 2024Article
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- RING-finger E3 ligases regulatory network in PI3K/AKT-mediated glucose metabolism.Cell death discovery · 2022Review
- Tetramethylpyrazine nitrone activates hypoxia-inducible factor and regulates iron homeostasis to improve renal anemia.Frontiers in pharmacology · 2022Article
- Nuclear Receptor-Mediated Metabolic Reprogramming and the Impact on HR+ Breast Cancer.Cancers · 2021Review
- Oestrogen receptors and hypoxia inducible factor 1 alpha expression in abdominal wall endometriosis.Reproductive biomedicine online · 2020Article
- Combined Aberrant Expression of NDRG2 and LDHA Predicts Hepatocellular Carcinoma Prognosis and Mediates the Anti-tumor Effect of Gemcitabine.International journal of biological sciences · 2019Article
- Crosstalk between Notch, HIF-1α and GPER in Breast Cancer EMT.International journal of molecular sciences · 2018Review
- Estrogen stabilizes hypoxia-inducible factor 1α through G protein-coupled estrogen receptor 1 in eutopic endometrium of endometriosis.Fertility and sterility · 2017Article
- Cold Inducible RNA Binding Protein Is Involved in Chronic Hypoxia Induced Neuron Apoptosis by Down-Regulating HIF-1α Expression and Regulated By microRNA-23a.International journal of biological sciences · 2017Article
- Targeting the long noncoding RNA MALAT1 blocks the pro-angiogenic effects of osteosarcoma and suppresses tumour growth.International journal of biological sciences · 2017Article
- Estrogen-dependent downregulation of hypoxia-inducible factor (HIF)-2α in invasive breast cancer cells.Oncotarget · 2016Article
- Targeting metabolism in breast cancer: How far we can go?World journal of clinical oncology · 2016Review
- Pheochromocytoma: Gasping for Air.Hormones & cancer · 2015Review
- mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging.Annals of the New York Academy of Sciences · 2015Review
- Membrane-initiated estradiol signaling of epithelial-mesenchymal transition-associated mechanisms through regulation of tight junctions in human breast cancer cells.Hormones & cancer · 2014Article
- Nonhypoxic regulation and role of hypoxia-inducible factor 1 in aromatase inhibitor resistant breast cancer.Breast cancer research : BCR · 2014Article
- The quinoxaline di-N-oxide DCQ blocks breast cancer metastasis in vitro and in vivo by targeting the hypoxia inducible factor-1 pathway.Molecular cancer · 2014Article
- Gerometabolites: the pseudohypoxic aging side of cancer oncometabolites.Cell cycle (Georgetown, Tex.) · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia-inducible factor 1 (HIF1) has been implicated in regulating many of the genes responsible for angiogenesis, erythropoiesis, glucose metabolism and cancer pathogenesis. In this study, we demonstrate that exposure of human breast cancer lines to 17β-oestradiol (E2) rapidly induced the expression of HIF-1α, the regulated subunit of HIF1, in normoxic condition. Hypoxia-inducible factor-1α is normally degraded in normoxia through ubiquitination-mediated proteolysis, whereas hypoxia modulates HIF-1α level by inhibiting ubiquitination-mediated degradation.
methodsOestradiol-induced accumulation of HIF-1α in breast cancer lines was detected by western blot analysis and its promoter activity was measured by HIF1 reporter assay. Molecular signalling of oestradiol-mediated HIF-1α expression was studied using specific pharmacological inhibitors and small interference RNA by co-immunoprecipitation and western blotting analysis.
resultsOestradiol has been observed to rapidly activate the nongenomic signalling cascade leading to HIF-1α protein synthesis. The results define a signalling pathway in breast cancer cells whereby oestradiol induces a rapid protein-protein interaction of ERα-c-Src-PI3K, resulting in the activation of PI3K/AKT pathway leading to mammalian target of rapamycin (mTOR) phosphorylation. The mTOR then stimulates translation by phosphorylating p70 S6 kinase and 4EB-P1, modulating HIF-1α protein synthesis. Oestradiol-stimulated HIF-1α activity was inhibited by either siRNA or pharmacological inhibitors to ERα, c-Src, PI3K and mTOR, providing a mechanism for the modulation of HIF-1α protein synthesis.
conclusionThese results show oestradiol-induced expression of HIF-1α, downstream of the ERα/c-Src/PI3K/AKT/mTOR pathway in human breast cancer cells.
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