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• W2116053967 abstract "// William J. Fredericks 1 , Jorge Sepulveda 2 , Priti Lal 3 , John E. Tomaszewski 4 , Ming-Fong Lin 5 , Terry McGarvey 6 , Frank J Rauscher III 7 , S. Bruce Malkowicz 1 1 Department of Surgery, Division of Urology, University of Pennsylvania and Veterans Affairs Medical Center Philadelphia, Philadelphia, PA 2 Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY. 3 Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA. 4 Department of Pathology and Anatomical Sciences, State University New York, Buffalo, NY. 5 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE. 6 Department of Anatomy, Kirksville Osteopathic Medical School, Kirksville, MO 7 The Wistar Institute, Philadelphia, PA. Correspondence: William J. Fredericks, email: // Frank J Rauscher III, email: // S. Bruce Malkowicz, email: // Keywords : TERE1, UBIAD1, prostate cancer, castrate resistant prostate cancer, CRPC, LnCaP, cholesterol, SXR, androgen catabolism, Vitamin K-2 Received : June 20, 2013 Accepted : July 5, 2013 Published : July 7, 2013 Abstract Castrate-Resistant Prostate Cancer (CRPC) is characterized by persistent androgen receptor-driven tumor growth in the apparent absence of systemic androgens. Current evidence suggests that CRPC cells can produce their own androgens from endogenous sterol precursors that act in an intracrine manner to stimulate tumor growth. The mechanisms by which CRPC cells become steroidogenic during tumor progression are not well defined. Herein we describe a novel link between the elevated cholesterol phenotype of CRPC and the TERE1 tumor suppressor protein, a prenyltransferase that synthesizes vitamin K-2, which is a potent endogenous ligand for the SXR nuclear hormone receptor. We show that 50% of primary and metastatic prostate cancer specimens exhibit a loss of TERE1 expression and we establish a correlation between TERE1 expression and cholesterol in the LnCaP-C81 steroidogenic cell model of the CRPC. LnCaP-C81 cells also lack TERE1 protein, and show elevated cholesterol synthetic rates, higher steady state levels of cholesterol, and increased expression of enzymes in the de novo cholesterol biosynthetic pathways than the non-steroidogenic prostate cancer cells. C81 cells also show decreased expression of the SXR nuclear hormone receptor and a panel of directly regulated SXR target genes that govern cholesterol efflux and steroid catabolism. Thus, a combination of increased synthesis, along with decreased efflux and catabolism likely underlies the CRPC phenotype: SXR might coordinately regulate this phenotype. Moreover, TERE1 controls synthesis of vitamin K-2, which is a potent endogenous ligand for SXR activation, strongly suggesting a link between TERE1 levels, K-2 synthesis and SXR target gene regulation. We demonstrate that following ectopic TERE1 expression or induction of endogenous TERE1, the elevated cholesterol levels in C81 cells are reduced. Moreover, reconstitution of TERE1 expression in C81 cells reactivates SXR and switches on a suite of SXR target genes that coordinately promote both cholesterol efflux and androgen catabolism. Thus, loss of TERE1 during tumor progression reduces K-2 levels resulting in reduced transcription of SXR target genes. We propose that TERE1 controls the CPRC phenotype by regulating the endogenous levels of Vitamin K-2 and hence the transcriptional control of a suite of steroidogenic genes via the SXR receptor. These data implicate the TERE1 protein as a previously unrecognized link affecting cholesterol and androgen accumulation that could govern acquisition of the CRPC phenotype." @default.
• W2116053967 created "2016-06-24" @default.
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• W2116053967 date "2013-07-07" @default.
• W2116053967 modified "2023-09-28" @default.
• W2116053967 title "The tumor suppressor TERE1 (UBIAD1) prenyltransferase regulates the elevated cholesterol phenotype in castration resistant prostate cancer by controlling a program of ligand dependent SXR target genes" @default.
• W2116053967 cites W1557632339 @default.
• W2116053967 cites W1963871654 @default.
• W2116053967 cites W1966367587 @default.
• W2116053967 cites W1971972260 @default.
• W2116053967 cites W1972090433 @default.
• W2116053967 cites W1973165542 @default.
• W2116053967 cites W1974235686 @default.
• W2116053967 cites W1976914747 @default.
• W2116053967 cites W1985439317 @default.
• W2116053967 cites W1986527803 @default.
• W2116053967 cites W1989225516 @default.
• W2116053967 cites W1991684218 @default.
• W2116053967 cites W1997156303 @default.
• W2116053967 cites W1998520443 @default.
• W2116053967 cites W1998792377 @default.
• W2116053967 cites W2005070872 @default.
• W2116053967 cites W2007951687 @default.
• W2116053967 cites W2010838601 @default.
• W2116053967 cites W2014393189 @default.
• W2116053967 cites W2022991915 @default.
• W2116053967 cites W2025165872 @default.
• W2116053967 cites W2025664742 @default.
• W2116053967 cites W2026194974 @default.
• W2116053967 cites W2028818304 @default.
• W2116053967 cites W2029145330 @default.
• W2116053967 cites W2030489986 @default.
• W2116053967 cites W2031775425 @default.
• W2116053967 cites W2035844078 @default.
• W2116053967 cites W2039031803 @default.
• W2116053967 cites W2039139292 @default.
• W2116053967 cites W2041612214 @default.
• W2116053967 cites W2042264135 @default.
• W2116053967 cites W2044400918 @default.
• W2116053967 cites W2048548143 @default.
• W2116053967 cites W2051818991 @default.
• W2116053967 cites W2057472767 @default.
• W2116053967 cites W2060378822 @default.
• W2116053967 cites W2068725665 @default.
• W2116053967 cites W2072782375 @default.
• W2116053967 cites W2073896237 @default.
• W2116053967 cites W2075379080 @default.
• W2116053967 cites W2075990265 @default.
• W2116053967 cites W2076021360 @default.
• W2116053967 cites W2080672215 @default.
• W2116053967 cites W2085444732 @default.
• W2116053967 cites W2085525100 @default.
• W2116053967 cites W2088676519 @default.
• W2116053967 cites W2094212146 @default.
• W2116053967 cites W2095111183 @default.
• W2116053967 cites W2095351093 @default.
• W2116053967 cites W2101314083 @default.
• W2116053967 cites W2114853793 @default.
• W2116053967 cites W2115420718 @default.
• W2116053967 cites W2127236616 @default.
• W2116053967 cites W2128179467 @default.
• W2116053967 cites W2133113317 @default.
• W2116053967 cites W2137996608 @default.
• W2116053967 cites W2140777784 @default.
• W2116053967 cites W2141569270 @default.
• W2116053967 cites W2142198156 @default.
• W2116053967 cites W2145137051 @default.
• W2116053967 cites W2145604196 @default.
• W2116053967 cites W2148416479 @default.
• W2116053967 cites W2150662398 @default.
• W2116053967 cites W2151371117 @default.
• W2116053967 cites W2154246409 @default.
• W2116053967 cites W2156048227 @default.
• W2116053967 cites W2157373298 @default.
• W2116053967 cites W2157711994 @default.
• W2116053967 cites W2157906581 @default.
• W2116053967 cites W2160390400 @default.
• W2116053967 cites W2161495150 @default.
• W2116053967 cites W2164978970 @default.
• W2116053967 cites W2165855078 @default.
• W2116053967 cites W2166526596 @default.
• W2116053967 cites W2171192504 @default.
• W2116053967 cites W2171996591 @default.
• W2116053967 cites W2313943705 @default.
• W2116053967 cites W2328105557 @default.
• W2116053967 cites W2328619742 @default.
• W2116053967 cites W4233116228 @default.
• W2116053967 cites W66881458 @default.
• W2116053967 doi "https://doi.org/10.18632/oncotarget.1103" @default.
• W2116053967 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3759667" @default.
• W2116053967 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23919967" @default.

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