ArticleBMC medicine2010
Hypoxia inducible factor 1alpha gene (HIF-1alpha) splice variants: potential prognostic biomarkers in breast cancer.
Article in BMC medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Associations between C1772T polymorphism in hypoxia-inducible factor-1α gene and breast cancer: a meta-analysis.Medical science monitor : international medical journal of experimental and clinical research · 2014Pooled it
- The effects of Berberis vulgaris consumption on plasma levels of IGF-1, IGFBPs, PPAR-γ and the expression of angiogenic genes in women with benign breast disease: a randomized controlled clinical trial.BMC complementary and alternative medicine · 2019Trial
- Alternative splicing rewires breast cancer and opens therapeutic avenues.Cell communication and signaling : CCS · 2026Review
- HIF-mediated hierarchical hypoxic adaptation, a novel paradigm in heart failure pathogenesis: is there a role for targeted therapies?Frontiers in pharmacology · 2026Review
- Hypoxia-mediated regulation of mRNA metabolism: from transcription to stability.Cell communication and signaling : CCS · 2025Review
- Hypoxia-inducible factors in breast cancer: prognostic indicators and emerging biomarkers: narrative review.Annals of medicine and surgery (2012) · 2025Review
- Aerobic exercise-induced HIF-1α upregulation in heart failure: exploring potential impacts on MCT1 and MPC1 regulation.Molecular medicine (Cambridge, Mass.) · 2024Article
- Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy.Cellular and molecular life sciences : CMLS · 2023Review
- Hypoxia-induced autophagy in triple negative breast cancer: association with prognostic variables, patients' survival and response to neoadjuvant chemotherapy.Virchows Archiv : an international journal of pathology · 2023Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Review
- Astragaloside IV protects cardiomyocytes against hypoxia injury viaAnnals of translational medicine · 2021Article
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
- Alternative splicing: Human disease and quantitative analysis from high-throughput sequencing.Computational and structural biotechnology journal · 2021Review
- Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Cross-Species Insights Into Genomic Adaptations to Hypoxia.Frontiers in genetics · 2020Review
- Regulation of Gene Expression under Hypoxic Conditions.International journal of molecular sciences · 2019Review
- The role of hypoxia-inducible factors in tumor angiogenesis and cell metabolism.Genes & diseases · 2017Review
- Preferential activation of HIF-2α adaptive signalling in neuronal-like cells in response to acute hypoxia.PloS one · 2017Article
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11 authors.
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Abstract
backgroundHypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1alpha protein overexpression has been shown in breast cancer. The impact of HIF-1alpha alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known.
methodsUsing real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1alpha and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1alpha splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival.
resultsHIF-1alpha isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1alphaTAG) and HIF-1alpha736 mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (P = 0.009 and P = 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1alphaTAG mRNA levels (P = 0.037). Significant statistical association was found between tumour grade and HIF-1alphaTAG (P = 0.048), and total HIF-1alpha (P = 0.048) mRNA levels. HIF-1alphaTAG mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (P = 0.005 and P = 0.033 respectively). Univariate analysis showed that high HIF-1alphaTAG mRNA levels correlated with shortened metastasis free survival (P = 0.01).
conclusionsOur results show for the first time that mRNA expression of a HIF-1alphaTAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.See commentary: http://www.biomedcentral.com/1741-7015/8/45.
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