title: Common reduction of the Raf kinase inhibitory protein in clear cell renal cell carcinoma.
abstract: Despite the recent progress in our understanding of clear cell renal cell carcinomas (ccRCCs), the etiology of ccRCC remains unclear. We reported here a prevailing reduction of the raf kinase inhibitory protein (RKIP) in ccRCC. In our examination of more than 600 ccRCC patients by western blot and immunohistochemistry, RKIP was significantly reduced in 80% of tumors. Inhibition of RKIP transcription in ccRCC occurs to greater levels than VHL transcription based on the quantification analysis of their transcripts in six large datasets of DNA microarray available in Oncomine™ with the median rank of suppression being 582 and 2343 for RKIP and VHL, respectively. Collectively, the magnitude of RKIP reduction and the levels of its downregulation match those of VHL. Furthermore, RKIP displays tumor suppressing activity in ccRCC. While modulation of RKIP expression did not affect the proliferation of A498 and 786-0 ccRCC cells and neither their ability to form xenograft tumors in NOD/SCID mice, ectopic expression or knockdown of RKIP inhibited or enhanced A498 and 786-0 ccRCC cell invasion, respectively. This was associated with robust changes in vimentin expression, a marker of EMT. Taken together, we demonstrate here that downregulation of RKIP occurs frequently at a rate that reaches that of VHL, suggesting RKIP being a critical tumor suppressor for ccRCC. This is consistent with RKIP being a tumor suppressor for other cancers.
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada, Hamilton, Ontario, Canada. Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada. The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Brianne
authors.initials: B
authors.lastname: Hill
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada, Hamilton, Ontario, Canada. Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada. The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: De Melo
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada, Hamilton, Ontario, Canada. Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada. The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Judy
authors.initials: J
authors.lastname: Yan
authors.affiliation: The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada. Division of Urology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Anil
authors.initials: A
authors.lastname: Kapoor
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada, Hamilton, Ontario, Canada. Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada. The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada. Department of Biological Chemistry and Molecular Pharmacology (BCMP), Harvard Medical School, Boston, MA, USA.
authors.forename: Lizhi
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Cutz
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada, Hamilton, Ontario, Canada. The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada. College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
authors.forename: Xingchang
authors.initials: X
authors.lastname: Feng
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada, Hamilton, Ontario, Canada. Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada. The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Nazihah
authors.initials: N
authors.lastname: Bakhtyar
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada, Hamilton, Ontario, Canada. Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada. The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology*; D013058:Mass Spectrometry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D049488:Phosphatidylethanolamine Binding Protein / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein