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Expression of Hypoxia Inducible Factor-1α and 2α in Genetically Distinct Early Renal Cortical Tumors

2006; Lippincott Williams & Wilkins; Volume: 175; Issue: 5 Linguagem: Inglês

10.1016/s0022-5347(05)00890-6

1527-3792

Chong M. Kim, Cathy D. Vocke, Carlos A. Torres‐Cabala, Youfeng Yang, Laura S. Schmidt, McClellan M. Walther, W. Marston Linehan,

High Altitude and Hypoxia

No AccessJournal of UrologyInvestigative urology1 May 2006Expression of Hypoxia Inducible Factor-1α and 2α in Genetically Distinct Early Renal Cortical Tumors Chong M. Kim, Cathy Vocke, Carlos Torres-Cabala, Youfeng Yang, Laura Schmidt, McClellan Walther, and W. Marston Linehan Chong M. KimChong M. Kim Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda , Cathy VockeCathy Vocke Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda , Carlos Torres-CabalaCarlos Torres-Cabala Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda , Youfeng YangYoufeng Yang Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda , Laura SchmidtLaura Schmidt Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute Frederick, Frederick, Maryland , McClellan WaltherMcClellan Walther Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda , and W. Marston LinehanW. Marston Linehan Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)00890-6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The role of the HIF class of transcription factors has been implicated to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF-1α and HIF-2α in genetically distinct early renal cortical tumors. Materials and Methods: Nascent renal tumors of distinct histology from patients with a hereditary renal tumor syndrome were characterized for HIF expression using high amplification immunohistochemistry. In addition, indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1α and 2α in clear cell renal carcinoma cells. Results: Clear cell RCC tumors from patients with von Hippel-Lindau disease strongly expressed HIF-1α and HIF-2α (10 of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with Birt-Hogg-Dubé syndrome expressed predominantly HIF-2α with weaker HIF-1α expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1α expression was not seen in type I papillary tumors from patients with hereditary papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary tumors (6 of 12) expressed HIF-2α. Conclusions: Differential patterns of HIF-1α and HIF-2α protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes. Consistent, simultaneous over expression of HIF-1α and HIF-2α appears to be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF-2α expression was found in all 3 renal cortical tumor subtypes, suggesting a pivotal role in renal cortical tumorigenesis. Differential function of HIF-1α vs HIF-2α is suggested by the distinct subcellular localization pattern of HIF-1α and HIF-2α in clear cell renal carcinoma cells. References 1 : Genetic basis of cancer of the kidney: disease-specific approaches to therapy. Clin Cancer Res2004; 10: 6282S. Google Scholar 2 : Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol Med2001; 7: 345. Google Scholar 3 : Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res1999; 59: 5830. 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Mol Cell Biol2003; 23: 4959. Google Scholar © 2006 by American Urological AssociationFiguresReferencesRelatedDetailsCited ByAtala A (2018) Re: Loss of PBRM1 Rescues VHL Dependent Replication Stress to Promote Renal CarcinogenesisJournal of Urology, VOL. 200, NO. 2, (247-247), Online publication date: 1-Aug-2018.Laguna M (2018) Re: ClearCode34: A Prognostic Risk Predictor for Localized Clear Cell Renal Cell CarcinomaJournal of Urology, VOL. 193, NO. 1, (71-72), Online publication date: 1-Jan-2015. Volume 175Issue 5May 2006Page: 1908-1914 Advertisement Copyright & Permissions© 2006 by American Urological AssociationKeywordsalpha subunithereditaryhypoxia-inducible factor 2neoplastic syndromeskidneykidney neoplasmshypoxia-inducible factor 1MetricsAuthor Information Chong M. Kim Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda More articles by this author Cathy Vocke Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda More articles by this author Carlos Torres-Cabala Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda More articles by this author Youfeng Yang Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda More articles by this author Laura Schmidt Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute Frederick, Frederick, Maryland More articles by this author McClellan Walther Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda More articles by this author W. Marston Linehan Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda More articles by this author Expand All Advertisement PDF DownloadLoading ...