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AIMS: The cellular response to hypoxia includes the hypoxia inducible factor (HIF)-induced transcription of genes involved in diverse processes such as glycolysis, angiogenesis and the growth of experimental tumours. Regulation of the level of hypoxia inducible factors 1alpha and 2alpha (HIF-1alpha and HIF-2alpha) is a primary determinant of HIF activity. Recent biochemical and candidate gene approach studies have led to the discovery of three HIF-regulatory prolyl hydroxylases, PHD-1, -2 and -3 and an asparaginyl hydroxylase, also known as FIH (factor inhibiting HIF). In this study, we raised and characterized monoclonal antibodies against PHD-1, PHD-2, PHD-3 and FIH. METHODS AND RESULTS: Immunohistochemistry of normal tissues with these monoclonal antibodies demonstrated a wide distribution in epithelial cells, stromal cells and leucocytes, with cytoplasmic staining predominating over nuclear staining. A preliminary study of tumours showed variable staining in tumour, stromal and inflammatory cells. While all tumour types showed some positive staining with each antibody, the overall pattern suggested a slight decrease in the amount of staining seen with PHD-1, -2 and -3 and an increase in FIH staining in neoplasia compared with corresponding normal tissues. CONCLUSIONS: These monoclonal antibodies will allow further larger scale studies to determine the significance of PHD and FIH expression in neoplasia.

Original publication




Journal article



Publication Date





602 - 610


Animals, Antibodies, Monoclonal, COS Cells, Cell Line, Cell Line, Tumor, Cercopithecus aethiops, Dioxygenases, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Hypoxia-Inducible Factor-Proline Dioxygenases, Immediate-Early Proteins, Immunohistochemistry, Mixed Function Oxygenases, Neoplasms, Procollagen-Proline Dioxygenase, Repressor Proteins, Tissue Distribution, Transcription Factors