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


CONCLUSIONS
In our series of breast cancer patients, aHIF, and not HIF-1alpha transcript, is a marker of poor prognosis.
Cayre
Anne
A
Department of Pathology and INSERM U484, Centre Jean Perrin, Clermont-Ferrand, France. anne.cayre@cjp.fr
Rossignol
Fabrice
F
Clottes
Eric
E
Penault-Llorca
Frédérique
F
D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D011237:Predictive Value of Tests; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020033:Protein Isoforms; D016372:RNA, Antisense; D012334:RNA, Neoplasm; D014157:Transcription Factors