Cargando…
Subcellular FIH-1 expression patterns in invasive breast cancer in relation to HIF-1α expression
BACKGROUND: Hypoxia Inducible Factor-1α (HIF-1α) expression in breast cancer is associated with a poor clinical outcome. HIF-1α shows two expression patterns: the canonical poor prognosis hypoxia-related perinecrotic pattern and a diffuse expression pattern that seems to have less downstream effects...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223342/ https://www.ncbi.nlm.nih.gov/pubmed/21732131 http://dx.doi.org/10.1007/s13402-011-0053-5 |
Sumario: | BACKGROUND: Hypoxia Inducible Factor-1α (HIF-1α) expression in breast cancer is associated with a poor clinical outcome. HIF-1α shows two expression patterns: the canonical poor prognosis hypoxia-related perinecrotic pattern and a diffuse expression pattern that seems to have less downstream effects and is clearly associated with poor survival. Factor-inhibiting hypoxia-inducible factor 1 (FIH-1) inhibits HIF-1 activity by hydroxylating the C-terminal trans-activation domain of the HIF-1α subunit, thus preventing HIF-1 from recruiting co-activators CPB/p300, which are important for inducing the transcription of target genes. The aim of this study was to investigate the expression patterns of FIH-1 in breast cancer and evaluate the relationship between FIH-1 and HIF-1α expression in breast cancer as a possible explanation for apparently less downstream effects of diffuse HIF-1α expression. METHODS: Tissue sections from 92 consecutive invasive breast carcinomas were stained by immunohistochemistry for FIH-1, HIF-1α, glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX). RESULTS: 45 cases overexpressed HIF-1α, 5 of which in a perinecrotic fashion while FIH-1 was positive in 73 of the 92 cases studied. Contrary to our expectations, three out of five cases with perinecrotic HIF-1α expression were also positive for FIH1. Cytoplasmic FIH-1 correlated with HIF-1α expression (P = 0.03) and tumor grade (P = 0.01). HIF-1α overexpression predicted poorer prognosis as usual (P = 0.02). FIH expression had no additional prognostic value to HIF-1α. CONCLUSIONS: FIH1 is expressed in the majority of invasive breast carcinomas and shows distinct subcellular localization patterns. FIH-1 expression does not seem to explain the proposed functional differences between diffuse and perinecrotic HIF-1α expression in breast cancer. |
---|