{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:51:26Z","timestamp":1791305486762,"version":"4.3.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,4,3]],"date-time":"2003-04-03T00:00:00Z","timestamp":1049328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2003,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We previously identified 9 genes (i.e., thymosin \u03b24, secreted protein acidic and rich in cysteine, Cap43, ceruloplasmin, serum amyloid A, heat shock protein 90, LOT1, osteopontin and casein kinase I\u03b3) that are more highly expressed in cancerous regions than in noncancerous regions in human renal cancers. In our study, we considered the possibility that the von Hippel\u2010Lindau (VHL) tumor suppressor gene might be able to affect the expression of these 9 genes in renal cancer cells. We first established 2 VHL\u2010positive cell lines, 786\/VHL\u20101 and 786\/VHL\u20102, after the introduction of wild\u2010type VHL into VHL\u2010negative renal cancer 786\u2010O cells. Of these 9 genes, expression of the <jats:italic>Cap43<\/jats:italic> gene was specifically downregulated by VHL. Expression of Cap43 was also much lower in 4 other VHL\u2010positive renal cancer cell lines than in VHL\u2010negative 786\u2010O cells. Cap43 promoter assays with several deletion or mutation constructs demonstrated that the Sp1 site in the element from \u2013286 base pairs (bp) to \u201362 bp was partly responsible for VHL\u2010induced suppression of the <jats:italic>Cap43<\/jats:italic> gene. Immunostaining analysis with human specimens of renal cancers demonstrated that the Cap43 protein was expressed in most cancer cells and macrophages. We also observed a marked and specific increase of <jats:italic>Cap43<\/jats:italic> mRNA levels in response to hypoxia or nickel in all VHL\u2010positive cell lines. Cellular expression of <jats:italic>Cap43<\/jats:italic> mRNA in response to hypoxia or nickel thus is closely associated with <jats:italic>VHL<\/jats:italic> gene expression in renal cancer cells. Although the function of the Cap43 protein remains unclear, the expression of Cap43 protein could be a molecular marker closely associated with VHL in renal cancer. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.11152","type":"journal-article","created":{"date-parts":[[2003,5,20]],"date-time":"2003-05-20T11:34:57Z","timestamp":1053430497000},"page":"803-810","source":"Crossref","is-referenced-by-count":57,"title":["Downregulation of <i>Cap43<\/i> gene by von Hippel\u2010Lindau tumor suppressor protein in human renal cancer 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