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Nuclear Localization of Factor Inhibitor Hypoxia-Inducible Factor in Prostate Cancer Is Associated With Poor Prognosis

2011; Lippincott Williams & Wilkins; Volume: 185; Issue: 4 Linguagem: Inglês

10.1016/j.juro.2010.12.001

1527-3792

Nadeem Shaida, Peter Chan, Helen Turley, Catherine M. Jones, Suresh Kanga, Robert W. Ritchie, Peter R. Malone, Adrian L. Harris, Stephen B. Fox,

Cancer, Lipids, and Metabolism

No AccessJournal of UrologyInvestigative Urology1 Apr 2011Nuclear Localization of Factor Inhibitor Hypoxia-Inducible Factor in Prostate Cancer Is Associated With Poor Prognosis Nadeem Shaida, Peter Chan, Helen Turley, Catherine M. Jones, Suresh Kanga, Robert W. Ritchie, Peter R. Malone, Adrian L. Harris, and Stephen B. Fox Nadeem ShaidaNadeem Shaida Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom , Peter ChanPeter Chan Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia , Helen TurleyHelen Turley Reading and Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom , Catherine M. JonesCatherine M. Jones Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom , Suresh KangaSuresh Kanga Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom , Robert W. RitchieRobert W. Ritchie Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom , Peter R. MalonePeter R. Malone Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom , Adrian L. HarrisAdrian L. Harris Cancer Research United Kingdom Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom , and Stephen B. FoxStephen B. Fox Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia View All Author Informationhttps://doi.org/10.1016/j.juro.2010.12.001AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We determined the role of factor inhibiting hypoxia-inducible factor-1 in prostate cancer specimens. Materials and Methods: A tissue microarray of 152 prostate cancers was constructed and stained for factor inhibiting hypoxia-inducible factor-1, hypoxia-inducible factor-1α and 2α, and glucose transporter 1 as a prototypical downstream target of hypoxia-inducible factor-1α. Correlation analysis was done between these variables, and between factor inhibiting hypoxia-inducible factor-1, and clinical and pathological variables, including prostate specific antigen as a surrogate of recurrence. Results: Factor inhibiting hypoxia-inducible factor-1 was expressed in the cytoplasm and/or the nucleus in 86.5% of tumors, including exclusive cytoplasmic expression in 51.3% and exclusive nuclear expression in 5.3%. Any nuclear and exclusive expression of factor inhibiting hypoxia-inducible factor was associated with poor prognosis on univariate analysis (p = 0.007 and 0.042, respectively). On multivariate analysis men with nuclear expression in tumors were twice as likely to experience recurrence (p = 0.034). Conclusions: Factor inhibiting hypoxia-inducible factor-1 is widely expressed in prostate tumors. Its differential subcellular expression suggests that regulation of its expression is an important factor in the activity of the hypoxia-inducible factor pathway. Its modulation may help treat hypoxia-inducible factor driven aggressive prostate cancer. References 1 : Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer2002; 2: 38. Google Scholar 2 : Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differentiation2008; 15: 635. Google Scholar 3 : C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell2001; 107: 43. Google Scholar 4 : Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases. 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More articles by this author Helen Turley Reading and Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom More articles by this author Catherine M. Jones Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom More articles by this author Suresh Kanga Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom More articles by this author Robert W. Ritchie Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom More articles by this author Peter R. Malone Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom More articles by this author Adrian L. Harris Cancer Research United Kingdom Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom More articles by this author Stephen B. Fox Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia More articles by this author Expand All Advertisement PDF downloadLoading ...