Cayre Anne, Rossignol Fabrice, Clottes Eric, Penault-Llorca Frédérique
Department of Pathology and INSERM U484, Centre Jean Perrin, Clermont-Ferrand, France.
Breast Cancer Res. 2003;5(6):R223-30. doi: 10.1186/bcr652. Epub 2003 Sep 26.
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.
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.
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.
In our series of breast cancer patients, aHIF, and not HIF-1alpha transcript, is a marker of poor prognosis.
缺氧诱导因子-1α（HIF-1α）是一种转录因子的组成部分，该转录因子可调节参与肿瘤代谢和血管适应缺氧的基因。一种缺少外显子14的剪接变体（sHIF-1α）编码一种截短的蛋白质，该蛋白质与正常的HIF-1α蛋白竞争，降低其活性。最近描述了一种与HIF-1α mRNA的3'-非翻译区互补的天然反义转录本（aHIF）。
我们采用半定量多重逆转录聚合酶链反应（RT-PCR）检测方法，评估了110例浸润性乳腺癌患者中HIF-1α、sHIF-1α和aHIF的转录本浓度。
我们发现HIF-1α与sHIF-1α、sHIF-1α与aHIF之间存在强正相关，而HIF-1α/sHIF-1α与aHIF之间存在负相关。在这一系列高危原发性乳腺癌中，单因素分析（P = 0.0038）和多因素分析（P = 0.0016）显示，aHIF转录本表达与无病生存期差相关。
在我们的乳腺癌患者系列中，aHIF而非HIF-1α转录本是预后不良的标志物。
