Document Detail

The osterix transcription factor down-regulates interleukin-1 alpha expression in mouse osteosarcoma cells.
MedLine Citation:
PMID:  18234967     Owner:  NLM     Status:  MEDLINE    
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.
Ying Cao; Shu-Fang Jia; Geetika Chakravarty; Benoit de Crombrugghe; Eugenie S Kleinerman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  6     ISSN:  1541-7786     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-31     Completed Date:  2008-03-27     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  119-26     Citation Subset:  IM    
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MeSH Terms
Binding Sites
Bone Neoplasms / genetics*
Cell Line, Tumor
Gene Expression Regulation, Neoplastic*
Interleukin-1alpha / genetics*
Mice, Inbred BALB C
Mutation / genetics
Osteoprotegerin / genetics
Osteosarcoma / genetics*,  pathology
Promoter Regions, Genetic / genetics
RNA, Small Interfering
Sp1 Transcription Factor / metabolism
Transcription Factors / genetics,  metabolism*
Transcription, Genetic
Grant Support
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/CA/NCI NIH HHS; R01 CA042992-24/CA/NCI NIH HHS
Reg. No./Substance:
0/Interleukin-1alpha; 0/Osteoprotegerin; 0/RNA, Small Interfering; 0/Sp1 Transcription Factor; 0/Transcription Factors; 0/osterix protein, mouse

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