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 its alpha-subunit, which increase during hypoxia. Recent studies showed that the HIF-1alpha gene was amplified in prostate cancer, leading to overexpression of HIF-1alpha at normoxia. The aim of this study was to evaluate the presence of HIF-1alpha gene amplifications in invasive breast cancer as an explanation for HIF-1alpha protein overexpression. METHODS: Protein and gene expression of HIF-1alpha were analyzed on a tissue microarray of 94 breast cancers by immunohistochemistry and fluorescent in situ hybridization (FISH), respectively. RESULTS: Overexpression of HIF-1alpha protein was found in 58/94 (62%) of patients. No amplifications of the HIF-1alpha gene were detected. CONCLUSION: Increased protein levels of HIF-1alpha are not associated with amplification of the HIF-1alpha gene in human breast cancer. Therefore, other mechanisms than gene amplification must be responsible for HIF-alpha overexpression at normoxia.
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 its alpha-subunit, which increase during hypoxia. Recent studies showed that the HIF-1alpha gene was amplified in prostate cancer, leading to overexpression of HIF-1alpha at normoxia. The aim of this study was to evaluate the presence of HIF-1alpha gene amplifications in invasive breast cancer as an explanation for HIF-1alpha protein overexpression. METHODS: Protein and gene expression of HIF-1alpha were analyzed on a tissue microarray of 94 breast cancers by immunohistochemistry and fluorescent in situ hybridization (FISH), respectively. RESULTS: Overexpression of HIF-1alpha protein was found in 58/94 (62%) of patients. No amplifications of the HIF-1alpha gene were detected. CONCLUSION: Increased protein levels of HIF-1alpha are not associated with amplification of the HIF-1alpha gene in humanbreast cancer. Therefore, other mechanisms than gene amplification must be responsible for HIF-alpha overexpression at normoxia.