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aHIF but not HIF-1alpha transcript is a poor prognostic marker in human breast cancer.

Abstract : BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is part of a transcriptional factor that regulates genes involved in metabolic and vascular adaptation of tumours to oxygen restriction. A splicing variant lacking exon 14 (sHIF-1alpha) encodes a truncated protein that competes with the normal HIF-1alpha protein, decreasing its activity. A natural antisense transcript (aHIF) complementary to the 3'-untranslated region of HIF-1alpha mRNA was described recently. METHODS: With a semiquantitative multiplex reverse transcriptase-PCR (RT-PCR) assay, we assessed transcript concentrations of HIF-1alpha, sHIF-1alpha and aHIF in 110 patients with invasive breast carcinoma. RESULTS: We found a strong positive association between HIF-1alpha and sHIF-1alpha, sHIF-1alpha and aHIF, and an inverse correlation between HIF-1alpha /sHIF-1alpha and aHIF. aHIF transcript expression was associated with poor disease-free survival in univariate (P = 0.0038) and multivariate (P = 0.0016) analyses in this series of high-risk primary breast carcinomas. CONCLUSION: In our series of breast cancer patients, aHIF, and not HIF-1alpha transcript, is a marker of poor prognosis.
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Anne Cayre, Fabrice Rossignol, Eric Clottes, Frédérique Penault-Llorca. aHIF but not HIF-1alpha transcript is a poor prognostic marker in human breast cancer.. Breast Cancer Research, BioMed Central, 2003, 5 (6), pp.R223-30. ⟨10.1186/bcr652⟩. ⟨inserm-00114572⟩



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