Document Detail


Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype.
MedLine Citation:
PMID:  15107826     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Malignant mesotheliomas (MMs) are aggressive tumors derived from mesothelial cells lining the lungs, pericardium and peritoneum, and are often associated with occupational asbestos exposure. Suppression subtractive hybridization was used to identify genes differentially expressed in MM cells compared to normal mesothelial cells. A gene, SEP15, encoding a 15-kDa selenium-containing protein was isolated using this approach and was subsequently shown to be downregulated in approximately 60% of MM cell lines and tumor specimens. A SEP15 polymorphic variant, 1125A, resides in the SECIS recognition element in the 3'-UTR and may influence the efficiency of Sec incorporation into the protein during translation. Since previous studies have implicated a potential role of the trace element selenium as a chemopreventive agent in animal models and in several types of human cancer, we investigated the effect of selenium on MM cells and its dependence on SEP15 genotype. Selenium was shown to inhibit cell growth and induce apoptosis in a dose-dependent manner in MM cells but had minimal effect on normal mesothelial cells. However, MM cells with downregulated SEP15 or the 1125A variant were somewhat less responsive to the growth inhibitory and apoptotic effects of selenium than MM cells expressing wild-type protein. RNAi-based knockdown studies demonstrated that SEP15 inhibition makes sensitive MM cells more resistant to selenium. These data imply that selenium may be useful as a chemopreventive agent in individuals at high risk of MM due to asbestos exposure, although those with the 1125A polymorphism may be less responsive to the protective benefits of dietary selenium supplementation.
Authors:
Sinoula Apostolou; Julian O Klein; Yasuhiro Mitsuuchi; Justin N Shetler; Poulikos I Poulikakos; Suresh C Jhanwar; Warren D Kruger; Joseph R Testa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  23     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-24     Completed Date:  2004-07-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  5032-40     Citation Subset:  IM    
Affiliation:
Human Genetics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Cell Division / drug effects,  genetics
Down-Regulation
Gene Frequency
Genetic Variation
Genotype
Humans
Loss of Heterozygosity
Mesothelioma / genetics*,  pathology
Proteins / genetics*
RNA, Small Interfering / pharmacology
Selenium / pharmacology*
Selenoproteins
Transfection
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA-06927/CA/NCI NIH HHS; CA-45745/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proteins; 0/RNA, Small Interfering; 0/SEP15 protein, human; 0/Selenoproteins; 7782-49-2/Selenium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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