You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2015MP47-17 REDUCED TERE1 (UBIAD1) PROTEIN EXPRESSION ASSOCIATES WITH MALIGNANT BUT NOT BENIGN RENAL CANCERS. ECTOPIC TERE1 EXPRESSION INDUCES SXR TARGET GENES REGULATING BONE REMODELING: RELEVANCE TO BONE METASTASIS. William Fredericks, Frank Rauscher, Priti Lal, and S. Bruce Malkowicz William FredericksWilliam Fredericks More articles by this author , Frank RauscherFrank Rauscher More articles by this author , Priti LalPriti Lal More articles by this author , and S. Bruce MalkowiczS. Bruce Malkowicz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1537AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have described the TERE1 protein as a tumor suppressor based on upon reduced expression in urological cancers, including half of human renal clear cell tumor specimens, and the inhibition of growth of tumor cell lines upon ectopic expression. The product of TERE1's prenyltransferase activity, vitamin K2, activates a suite of SXR target genes promoting cholesterol efflux and fatty acid metabolism. Our objective was to extend the TERE1 expression analysis to other renal cancer subtypes and explore whether the TERE1/SXR axis affects a gene expression pattern with potential to modulate the tumor/bone microenvironment as has been described for Vitamin K2 and analogs. METHODS A Renal Cancer TMA of 132 lesions was evaluated for TERE1 expression by immunohistochemistry. TERE1 dosage was manipulated by cDNA adenovirus transduced to Caki-1 and Caki-2 renal cancer cell lines. Gene expression was analyzed by TAQman RT-PCR. RESULTS Of 132 Renal Carcinoma lesions, TERE1 expression was reduced or absent in each of the malignant subtypes: 53% (40/76) of Clear Cell, 32% (6/19) of Papillary, and 39% (7/18) of Chromophobe specimens, compared to 5% (1/16) of Benign Oncocytoma suggesting a correlation with malignant potential. TERE1-induced up to 10-fold changes in expression of a panel of 24 genes including SXR targets, Bone Gla protein genes, osteoblastic, and osteoclastic genes in Caki-1 and Caki-2 cell lines. TERE1 suppressed RANKL, important for induction of osteoclastic activity, as well as SXR and many of the osteoblastic SXR target genes (COLIA1, IBSP, MATN2, MSX2, ALPL, OSN) in Caki-1 cells. TERE1 activated RANKL and SXR and its targets (RANKL, COLIA1, IBSP, OPG, MSX2, TSK, STC2, MGP) in Caki-2 cells. Future studies will compare how these opposing expression patterns affect osteolytic activity in vitro and in vivo. CONCLUSIONS Renal cancers frequently metastasize to bone and typically produce osteolytic metastases. Understanding the role TERE1 plays in the metastatic microenvironment of bone may lead to therapy that inhibits metastasis to bone, or counters the severe skeletal related events associated with profound morbidity. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e558 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information William Fredericks More articles by this author Frank Rauscher More articles by this author Priti Lal More articles by this author S. Bruce Malkowicz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...