{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:28:10Z","timestamp":1791181690314,"version":"4.1.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2007,4,1]],"date-time":"2007-04-01T00:00:00Z","timestamp":1175385600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T00:00:00Z","timestamp":1374019200000},"content-version":"vor","delay-in-days":2299,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cell"],"published-print":{"date-parts":[[2007,4]]},"DOI":"10.1016\/j.ccr.2007.02.005","type":"journal-article","created":{"date-parts":[[2007,4,25]],"date-time":"2007-04-25T18:20:47Z","timestamp":1177525247000},"page":"311-319","source":"Crossref","is-referenced-by-count":163,"title":["Targeted Inactivation of Fh1 Causes Proliferative Renal Cyst Development and Activation of the Hypoxia Pathway"],"prefix":"10.1016","volume":"11","author":[{"given":"Patrick J.","family":"Pollard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Spencer-Dene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Shukla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley","family":"Howarth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Nye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"El-Bahrawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maesha","family":"Deheragoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Joannou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Igarashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Varsani-Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Rosewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Poulsom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Maxwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon W.","family":"Stamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P.M.","family":"Tomlinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ccr.2007.02.005_bib1","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/hmg\/ddg148","article-title":"Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency","volume":"12","author":"Alam","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ccr.2007.02.005_bib2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1365-2133.2005.06678.x","article-title":"Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer","volume":"153","author":"Alam","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"10.1016\/j.ccr.2007.02.005_bib3","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1136\/jmg.39.3.178","article-title":"Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas","volume":"39","author":"Baysal","year":"2002","journal-title":"J. Med. Genet."},{"key":"10.1016\/j.ccr.2007.02.005_bib4","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1749-6632.2001.tb03645.x","article-title":"Effect of L-carnitine pretreatment on 3-nitropropionic acid-induced inhibition of rat brain succinate dehydrogenase activity","volume":"939","author":"Binienda","year":"2001","journal-title":"Ann. N Y Acad. Sci."},{"key":"10.1016\/j.ccr.2007.02.005_bib5","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1046\/j.0022-3042.2001.00756.x","article-title":"Glucose deprivation and hypoxia increase the expression of the GLUT1 glucose transporter via a specific mRNA cis-acting regulatory element","volume":"80","author":"Boado","year":"2002","journal-title":"J. Neurochem."},{"key":"10.1016\/j.ccr.2007.02.005_bib6","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/28867","article-title":"Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis","volume":"394","author":"Carmeliet","year":"1998","journal-title":"Nature"},{"key":"10.1016\/j.ccr.2007.02.005_bib7","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1086\/324413","article-title":"The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway","volume":"69","author":"Gimenez-Roqueplo","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ccr.2007.02.005_bib8","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1210\/jc.2002-020525","article-title":"Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma","volume":"87","author":"Gimenez-Roqueplo","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ccr.2007.02.005_bib9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/08977199609034571","article-title":"Expression of trefoil peptides in the gastric mucosa of transgenic mice overexpressing transforming growth factor-alpha","volume":"13","author":"Goldenring","year":"1996","journal-title":"Growth Factors"},{"key":"10.1016\/j.ccr.2007.02.005_bib10","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1073\/pnas.0505903103","article-title":"Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission","volume":"103","author":"Greaves","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ccr.2007.02.005_bib11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/molehr\/7.3.255","article-title":"Vascular endothelial growth factor transgenic mice exhibit reduced male fertility and placental rejection","volume":"7","author":"Huminiecki","year":"2001","journal-title":"Mol. Hum. Reprod."},{"key":"10.1016\/j.ccr.2007.02.005_bib12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF03401807","article-title":"The molecular basis of von Hippel-Lindau disease","volume":"3","author":"Iliopoulos","year":"1997","journal-title":"Mol. Med."},{"key":"10.1016\/j.ccr.2007.02.005_bib13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ccr.2005.06.017","article-title":"HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: Novel role of fumarate in regulation of HIF stability","volume":"8","author":"Isaacs","year":"2005","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ccr.2007.02.005_bib14","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing","volume":"292","author":"Ivan","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.ccr.2007.02.005_bib15","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1126\/science.1059796","article-title":"Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation","volume":"292","author":"Jaakkola","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.ccr.2007.02.005_bib16","doi-asserted-by":"crossref","first-page":"869","DOI":"10.2174\/1566524043359638","article-title":"Hereditary leiomyomatosis and renal cell cancer (HLRCC)","volume":"4","author":"Kiuru","year":"2004","journal-title":"Curr. Mol. Med."},{"key":"10.1016\/j.ccr.2007.02.005_bib17","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/S0002-9440(10)61757-9","article-title":"Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology","volume":"159","author":"Kiuru","year":"2001","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.ccr.2007.02.005_bib18","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.3748\/wjg.v11.i17.2616","article-title":"Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa","volume":"11","author":"Kivela","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.ccr.2007.02.005_bib19","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1136\/jmg.2005.036400","article-title":"Increased risk of cancer in patients with fumarate hydratase germline mutation","volume":"43","author":"Lehtonen","year":"2005","journal-title":"J. Med. Genet."},{"key":"10.1016\/j.ccr.2007.02.005_bib20","doi-asserted-by":"crossref","first-page":"25492","DOI":"10.1074\/jbc.271.41.25492","article-title":"Hypoxia-inducible protein binding to vascular endothelial growth factor mRNA and its modulation by the von Hippel-Lindau protein","volume":"271","author":"Levy","year":"1996","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ccr.2007.02.005_bib21","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1101\/gad.13.14.1822","article-title":"The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity","volume":"13","author":"Lisztwan","year":"1999","journal-title":"Genes Dev."},{"key":"10.1016\/j.ccr.2007.02.005_bib22","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/00005792-199711000-00001","article-title":"von Hippel-Lindau disease","volume":"76","author":"Maher","year":"1997","journal-title":"Medicine (Baltimore)"},{"key":"10.1016\/j.ccr.2007.02.005_bib23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1535-6108(02)00071-5","article-title":"HIF activation identifies early lesions in VHL kidneys: Evidence for site-specific tumor suppressor function in the nephron","volume":"1","author":"Mandriota","year":"2002","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ccr.2007.02.005_bib24","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1242\/jcs.00655","article-title":"HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O(2) levels","volume":"116","author":"Masson","year":"2003","journal-title":"J.\u00a0Cell Sci."},{"key":"10.1016\/j.ccr.2007.02.005_bib25","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/20459","article-title":"The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis","volume":"399","author":"Maxwell","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.ccr.2007.02.005_bib26","series-title":"Manipulating the Mouse Embryo: A Laboratory Manual","author":"Nagy","year":"2003"},{"key":"10.1016\/j.ccr.2007.02.005_bib27","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/path.1686","article-title":"Evidence of increased microvessel density and activation of the hypoxia pathway in tumours from the hereditary leiomyomatosis and renal cell cancer syndrome","volume":"205","author":"Pollard","year":"2005","journal-title":"J. Pathol."},{"key":"10.1016\/j.ccr.2007.02.005_bib28","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1093\/hmg\/ddi227","article-title":"Accumulation of Krebs cycle intermediates and over-expression of HIF1{alpha} in tumours which result from germline FH and SDH mutations","volume":"14","author":"Pollard","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ccr.2007.02.005_bib29","first-page":"121","article-title":"A robust method for isotopic riboprobe in situ hybridisation to localise mRNAs in routine pathology specimens","volume":"42","author":"Poulsom","year":"1998","journal-title":"Eur. J. Histochem."},{"key":"10.1016\/j.ccr.2007.02.005_bib30","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nm0603-677","article-title":"Regulation of angiogenesis by hypoxia: Role of the HIF system","volume":"9","author":"Pugh","year":"2003","journal-title":"Nat. Med."},{"key":"10.1016\/j.ccr.2007.02.005_bib31","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1128\/MCB.25.8.3163-3172.2005","article-title":"Inactivation of the arylhydrocarbon receptor nuclear translocator (Arnt) suppresses von Hippel-Lindau disease-associated vascular tumors in mice","volume":"25","author":"Rankin","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.ccr.2007.02.005_bib32","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1158\/0008-5472.CAN-05-3241","article-title":"Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor","volume":"66","author":"Rankin","year":"2006","journal-title":"Cancer Res."},{"key":"10.1016\/j.ccr.2007.02.005_bib33","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1128\/MCB.25.13.5675-5686.2005","article-title":"Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma","volume":"25","author":"Raval","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.ccr.2007.02.005_bib34","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nrm1366","article-title":"Oxygen sensing by HIF hydroxylases","volume":"5","author":"Schofield","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ccr.2007.02.005_bib35","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ccr.2004.11.022","article-title":"Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase","volume":"7","author":"Selak","year":"2005","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ccr.2007.02.005_bib36","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1097\/01.ASN.0000016443.50138.CD","article-title":"A minimal Ksp-cadherin promoter linked to a green fluorescent protein reporter gene exhibits tissue-specific expression in the developing kidney and genitourinary tract","volume":"13","author":"Shao","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.ccr.2007.02.005_bib37","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1097\/01.ASN.0000016444.90348.50","article-title":"Epithelial-specific Cre\/lox recombination in the developing kidney and genitourinary tract","volume":"13","author":"Shao","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.ccr.2007.02.005_bib38","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0002-9440(10)64554-3","article-title":"The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages","volume":"157","author":"Talks","year":"2000","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.ccr.2007.02.005_bib39","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1172\/JCI19435","article-title":"Mitochondrial DNA mutations in human colonic crypt stem cells","volume":"112","author":"Taylor","year":"2003","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ccr.2007.02.005_bib40","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/ng849","article-title":"Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer","volume":"30","author":"Tomlinson","year":"2002","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ccr.2007.02.005_bib41","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1086\/376435","article-title":"Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America","volume":"73","author":"Toro","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ccr.2007.02.005_bib42","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","article-title":"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension","volume":"92","author":"Wang","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ccr.2007.02.005_bib43","first-page":"7075","article-title":"Hypoxia-inducible expression of tumor-associated carbonic anhydrases","volume":"60","author":"Wykoff","year":"2000","journal-title":"Cancer Res."},{"key":"10.1016\/j.ccr.2007.02.005_bib44","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/S0090-4295(01)01607-7","article-title":"Positive expression of HIF-2alpha\/EPAS1 in invasive bladder cancer","volume":"59","author":"Xia","year":"2002","journal-title":"Urology"},{"key":"10.1016\/j.ccr.2007.02.005_bib45","doi-asserted-by":"crossref","first-page":"8554","DOI":"10.1158\/1078-0432.CCR-0946-03","article-title":"Prognostic impact of hypoxia-inducible factors 1alpha and 2alpha in colorectal cancer patients: correlation with tumor angiogenesis and cyclooxygenase-2 expression","volume":"10","author":"Yoshimura","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ccr.2007.02.005_bib46","first-page":"1124","article-title":"Relative vulnerability of dopamine and GABA neurons in mesencephalic culture to inhibition of succinate dehydrogenase by malonate and 3-nitropropionic acid and protection by NMDA receptor blockade","volume":"275","author":"Zeevalk","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Cancer Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S153561080700058X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S153561080700058X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,4,27]],"date-time":"2019-04-27T13:53:44Z","timestamp":1556373224000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S153561080700058X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2007,4]]}},"alternative-id":["S153561080700058X"],"URL":"https:\/\/doi.org\/10.1016\/j.ccr.2007.02.005","relation":{},"ISSN":["1535-6108"],"issn-type":[{"value":"1535-6108","type":"print"}],"subject":[],"published":{"date-parts":[[2007,4]]}}}