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  • 1
    Publikationsdatum: 2013-11-30
    Beschreibung: Hypercholesterolemia is a risk factor for estrogen receptor (ER)-positive breast cancers and is associated with a decreased response of tumors to endocrine therapies. Here, we show that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol and an ER and liver X receptor (LXR) ligand, increases ER-dependent growth and LXR-dependent metastasis in mouse models of breast cancer. The effects of cholesterol on tumor pathology required its conversion to 27HC by the cytochrome P450 oxidase CYP27A1 and were attenuated by treatment with CYP27A1 inhibitors. In human breast cancer specimens, CYP27A1 expression levels correlated with tumor grade. In high-grade tumors, both tumor cells and tumor-associated macrophages exhibited high expression levels of the enzyme. Thus, lowering circulating cholesterol levels or interfering with its conversion to 27HC may be a useful strategy to prevent and/or treat breast cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899689/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899689/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nelson, Erik R -- Wardell, Suzanne E -- Jasper, Jeff S -- Park, Sunghee -- Suchindran, Sunil -- Howe, Matthew K -- Carver, Nicole J -- Pillai, Ruchita V -- Sullivan, Patrick M -- Sondhi, Varun -- Umetani, Michihisa -- Geradts, Joseph -- McDonnell, Donald P -- K99CA172357/CA/NCI NIH HHS/ -- R37 DK048807/DK/NIDDK NIH HHS/ -- R37DK048807/DK/NIDDK NIH HHS/ -- T32 CA059365/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 29;342(6162):1094-8. doi: 10.1126/science.1241908.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24288332" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Breast Neoplasms/blood/*metabolism/*pathology ; Cell Line, Tumor ; Cholestanetriol 26-Monooxygenase/antagonists & inhibitors/metabolism ; Disease Models, Animal ; Female ; Humans ; Hydroxycholesterols/antagonists & inhibitors/blood/*metabolism ; Hypercholesterolemia/blood/*metabolism ; Lung Neoplasms/secondary ; Mice ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2013-04-19
    Beschreibung: Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howe, Kerstin -- Clark, Matthew D -- Torroja, Carlos F -- Torrance, James -- Berthelot, Camille -- Muffato, Matthieu -- Collins, John E -- Humphray, Sean -- McLaren, Karen -- Matthews, Lucy -- McLaren, Stuart -- Sealy, Ian -- Caccamo, Mario -- Churcher, Carol -- Scott, Carol -- Barrett, Jeffrey C -- Koch, Romke -- Rauch, Gerd-Jorg -- White, Simon -- Chow, William -- Kilian, Britt -- Quintais, Leonor T -- Guerra-Assuncao, Jose A -- Zhou, Yi -- Gu, Yong -- Yen, Jennifer -- Vogel, Jan-Hinnerk -- Eyre, Tina -- Redmond, Seth -- Banerjee, Ruby -- Chi, Jianxiang -- Fu, Beiyuan -- Langley, Elizabeth -- Maguire, Sean F -- Laird, Gavin K -- Lloyd, David -- Kenyon, Emma -- Donaldson, Sarah -- Sehra, Harminder -- Almeida-King, Jeff -- Loveland, Jane -- Trevanion, Stephen -- Jones, Matt -- Quail, Mike -- Willey, Dave -- Hunt, Adrienne -- Burton, John -- Sims, Sarah -- McLay, Kirsten -- Plumb, Bob -- Davis, Joy -- Clee, Chris -- Oliver, Karen -- Clark, Richard -- Riddle, Clare -- Elliot, David -- Threadgold, Glen -- Harden, Glenn -- Ware, Darren -- Begum, Sharmin -- Mortimore, Beverley -- Kerry, Giselle -- Heath, Paul -- Phillimore, Benjamin -- Tracey, Alan -- Corby, Nicole -- Dunn, Matthew -- Johnson, Christopher -- Wood, Jonathan -- Clark, Susan -- Pelan, Sarah -- Griffiths, Guy -- Smith, Michelle -- Glithero, Rebecca -- Howden, Philip -- Barker, Nicholas -- Lloyd, Christine -- Stevens, Christopher -- Harley, Joanna -- Holt, Karen -- Panagiotidis, Georgios -- Lovell, Jamieson -- Beasley, Helen -- Henderson, Carl -- Gordon, Daria -- Auger, Katherine -- Wright, Deborah -- Collins, Joanna -- Raisen, Claire -- Dyer, Lauren -- Leung, Kenric -- Robertson, Lauren -- Ambridge, Kirsty -- Leongamornlert, Daniel -- McGuire, Sarah -- Gilderthorp, Ruth -- Griffiths, Coline -- Manthravadi, Deepa -- Nichol, Sarah -- Barker, Gary -- Whitehead, Siobhan -- Kay, Michael -- Brown, Jacqueline -- Murnane, Clare -- Gray, Emma -- Humphries, Matthew -- Sycamore, Neil -- Barker, Darren -- Saunders, David -- Wallis, Justene -- Babbage, Anne -- Hammond, Sian -- Mashreghi-Mohammadi, Maryam -- Barr, Lucy -- Martin, Sancha -- Wray, Paul -- Ellington, Andrew -- Matthews, Nicholas -- Ellwood, Matthew -- Woodmansey, Rebecca -- Clark, Graham -- Cooper, James D -- Tromans, Anthony -- Grafham, Darren -- Skuce, Carl -- Pandian, Richard -- Andrews, Robert -- Harrison, Elliot -- Kimberley, Andrew -- Garnett, Jane -- Fosker, Nigel -- Hall, Rebekah -- Garner, Patrick -- Kelly, Daniel -- Bird, Christine -- Palmer, Sophie -- Gehring, Ines -- Berger, Andrea -- Dooley, Christopher M -- Ersan-Urun, Zubeyde -- Eser, Cigdem -- Geiger, Horst -- Geisler, Maria -- Karotki, Lena -- Kirn, Anette -- Konantz, Judith -- Konantz, Martina -- Oberlander, Martina -- Rudolph-Geiger, Silke -- Teucke, Mathias -- Lanz, Christa -- Raddatz, Gunter -- Osoegawa, Kazutoyo -- Zhu, Baoli -- Rapp, Amanda -- Widaa, Sara -- Langford, Cordelia -- Yang, Fengtang -- Schuster, Stephan C -- Carter, Nigel P -- Harrow, Jennifer -- Ning, Zemin -- Herrero, Javier -- Searle, Steve M J -- Enright, Anton -- Geisler, Robert -- Plasterk, Ronald H A -- Lee, Charles -- Westerfield, Monte -- de Jong, Pieter J -- Zon, Leonard I -- Postlethwait, John H -- Nusslein-Volhard, Christiane -- Hubbard, Tim J P -- Roest Crollius, Hugues -- Rogers, Jane -- Stemple, Derek L -- 095908/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- 1 R01 DK55377-01A1/DK/NIDDK NIH HHS/ -- P01 HD022486/HD/NICHD NIH HHS/ -- P01 HD22486/HD/NICHD NIH HHS/ -- R01 GM085318/GM/NIGMS NIH HHS/ -- R01 OD011116/OD/NIH HHS/ -- R01 RR010715/RR/NCRR NIH HHS/ -- R01 RR020833/RR/NCRR NIH HHS/ -- England -- Nature. 2013 Apr 25;496(7446):498-503. doi: 10.1038/nature12111. Epub 2013 Apr 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23594743" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Chromosomes/genetics ; Conserved Sequence/*genetics ; Evolution, Molecular ; Female ; Genes/genetics ; Genome/*genetics ; Genome, Human/genetics ; Genomics ; Humans ; Male ; Meiosis/genetics ; Molecular Sequence Annotation ; Pseudogenes/genetics ; Reference Standards ; Sex Determination Processes/genetics ; Zebrafish/*genetics ; Zebrafish Proteins/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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