| The osterix transcription factor down-regulates interleukin-1 alpha expression in mouse osteosarcoma cells. | |
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MedLine Citation:
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PMID: 18234967 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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K7M2 mouse osteosarcoma cells form lytic tumors and are deficient in osterix (Osx), a zinc finger-containing transcription factor required for osteoblast differentiation and bone formation. Our previous studies showed that replacement of Osx suppresses lytic bone destruction. Cytokines, including interleukin (IL)-1alpha, IL-6, IL-11, and prostaglandin E2, have been shown to stimulate osteoclast activity. We showed that IL-1alpha production by K7M2 cells was significantly suppressed following Osx transfection through a transcription-mediated mechanism. Osx had no effect on IL-6, IL-11, or prostaglandin E2. Site-directed mutagenesis and chromatin immunoprecipitation indicated that Osx down-regulated IL-1alpha through an Sp1-binding site on the IL-1alpha promoter. Inhibiting Osx by small interfering RNA in two cell lines (Dunn and DLM8) that expressed high levels of Osx led to enhanced IL-1alpha promoter activity and protein production and altered the phenotype from blastic to lytic. These data suggest that Osx down-regulates IL-1alpha expression in mouse osteosarcoma cells via transcriptional repression of IL-1alpha and this may in turn affect the lytic activity of the tumor cells. |
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Authors:
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Ying Cao; Shu-Fang Jia; Geetika Chakravarty; Benoit de Crombrugghe; Eugenie S Kleinerman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cancer research : MCR Volume: 6 ISSN: 1541-7786 ISO Abbreviation: Mol. Cancer Res. Publication Date: 2008 Jan |
Date Detail:
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Created Date: 2008-01-31 Completed Date: 2008-03-27 Revised Date: 2011-05-16 |
Medline Journal Info:
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Nlm Unique ID: 101150042 Medline TA: Mol Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 119-26 Citation Subset: IM |
Affiliation:
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Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding Sites Bone Neoplasms / genetics* Cell Line, Tumor Down-Regulation* Gene Expression Regulation, Neoplastic* Interleukin-1alpha / genetics* Male Mice Mice, Inbred BALB C Mutation / genetics Osteoprotegerin / genetics Osteosarcoma / genetics*, pathology Phenotype Promoter Regions, Genetic / genetics RNA, Small Interfering Sp1 Transcription Factor / metabolism Transcription Factors / genetics, metabolism* Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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CA 16672/CA/NCI NIH HHS; CA 42992/CA/NCI NIH HHS; P30 CA016672-27/CA/NCI NIH HHS; P30 CA016672-35/CA/NCI NIH HHS; R01 CA042992-24/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-1alpha; 0/Osteoprotegerin; 0/RNA, Small Interfering; 0/Sp1 Transcription Factor; 0/Transcription Factors; 0/osterix protein, mouse |
| Comments/Corrections | |
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