No Amplifications of Hypoxia-Inducible Factor-1αGene in Invasive Breast Cancer: A Tissue Microarray Study

摘要

Objective: Hypoxia Inducible Factor‐1 (HIF‐1) is an important transcription factor that stimulates tumour growth and metastases via several pathways, including angiogenesis and altered metabolism. Activation of HIF‐1 depends on the levels of itsα‐subunit, which increase during hypoxia. Recent studies showed that the HIF‐1αgene was amplified in prostate cancer, leading to overexpression of HIF‐1αat normoxia. The aim of this study was to evaluate the presence of HIF‐1αgene amplifications in invasive breast cancer as an explanation for HIF‐1αprotein overexpression.Methods: Protein and gene expression of HIF‐1αwere analyzed on a tissue microarray of 94 breast cancers by immunohistochemistry and fluorescent in situ hybridization (FISH), respectively.Results: Overexpression of HIF‐1αprotein was found in 58/94 (62%) of patients. No amplifications of the HIF‐1αgene were detected.Conclusion: Increased protein levels of HIF‐1αare not associated with amplification of the HIF‐1αgene in human breast cancer. Therefore, other mechanisms than gene amplification must be responsible for HIF‐αoverexpression at normoxia.