Loss of PL6 protein expression in renal clear cell carcinomas and other VHL-deficient tumours

A. V. Ivanova, A. Vortmeyer, S. V. Ivanov, M. L. Nickerson, E. R. Maher, M. I. Lerman

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Mutations in the von Hippel-Lindau tumour suppressor gene (VHL) cause the VHL hereditary cancer syndrome and occur in most sporadic clear cell renal cell cancers (CC-RCCs). The mechanisms by which VHL loss of function promotes tumour development in the kidney are not fully elucidated. Here, we analyse expression of PL6, one of the potential tumour suppressor genes from the critical 3p21.3 region involved in multiple common cancers. We classify PL6 as a Golgi-resident protein based on its perinuclear colocalization with GPP130 in all cells and tissues analysed. We show that PL6 RNA and protein expression is completely or partially lost in all analysed CC-RCCs and other VHL-deficient tumours studied, including the early precancerous lesions in VHL disease. The restoration of VHL function in vitro in the VHL-deficient CC-RCC cell lines was found to reinstate PL6 expression, thus establishing a direct link between VHL and PL6. Insensitivity of PL6 to hypoxia suggested that PL6 is regulated by VHL via a HIF-1-independent pathway. We ruled out mutations and promoter methylation as possible causes of PL6 down-regulation in CC-RCC. 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.

Original languageEnglish (US)
Pages (from-to)46-57
Number of pages12
JournalJournal of Pathology
Volume214
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • CC-RCC
  • Golgi
  • PL6
  • Tumour suppressor
  • VHL

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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