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No amplifications of hypoxia-inducible factor-1α gene in invasive breast cancer: A tissue microarray study

By M.M. Vleugel, R. Bos, Horst Buerger, P. van der Groep, O.R. Saramäki, T. Visakorpi, E. van der Wall and P.J. van Diest


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

Topics: Geneeskunde, HIF-1α, gene expression, amplification,, immunohistochemistry, breast cancer, FISH
Year: 2004
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