{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:39:03Z","timestamp":1789047543872,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,10,31]],"date-time":"2007-10-31T00:00:00Z","timestamp":1193788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the von Hippel\u2013Lindau tumour suppressor gene (<jats:italic>VHL<\/jats:italic>) cause the VHL hereditary cancer syndrome and occur in most sporadic clear cell renal cell cancers (CC\u2010RCCs). The mechanisms by which <jats:italic>VHL<\/jats:italic> loss of function promotes tumour development in the kidney are not fully elucidated. Here, we analyse expression of <jats:italic>PL6<\/jats:italic>, one of the potential tumour suppressor genes from the critical 3p21.3 region involved in multiple common cancers. We classify PL6 as a Golgi\u2010resident protein based on its perinuclear co\u2010localization with GPP130 in all cells and tissues analysed. We show that <jats:italic>PL6<\/jats:italic> RNA and protein expression is completely or partially lost in all analysed CC\u2010RCCs and other VHL\u2010deficient tumours studied, including the early precancerous lesions in VHL disease. The restoration of <jats:italic>VHL<\/jats:italic> function <jats:italic>in vitro<\/jats:italic> in the <jats:italic>VHL<\/jats:italic>\u2010deficient CC\u2010RCC cell lines was found to reinstate PL6 expression, thus establishing a direct link between <jats:italic>VHL<\/jats:italic> and <jats:italic>PL6<\/jats:italic>. Insensitivity of <jats:italic>PL6<\/jats:italic> to hypoxia suggested that PL6 is regulated by VHL via a HIF\u20101\u2010independent pathway. We ruled out mutations and promoter methylation as possible causes of <jats:italic>PL6<\/jats:italic> down\u2010regulation in CC\u2010RCC. We hypothesize that loss of a putative PL6 secretory function due to VHL deficiency is an early and important event that may promote tumour initiation and growth. Copyright \u00a9 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2252","type":"journal-article","created":{"date-parts":[[2007,10,31]],"date-time":"2007-10-31T12:17:06Z","timestamp":1193833026000},"page":"46-57","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Loss of PL6 protein expression in renal clear cell carcinomas and other <i>VHL<\/i>\u2010deficient tumours"],"prefix":"10.1002","volume":"214","author":[{"given":"AV","family":"Ivanova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Vortmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SV","family":"Ivanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ML","family":"Nickerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ER","family":"Maher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MI","family":"Lerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,10,31]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.273.7.558"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202349"},{"issue":"21","key":"e_1_2_7_4_2","first-page":"6116","article-title":"The 630 kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. 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