Source:http://linkedlifedata.com/resource/pubmed/id/17178897
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24
|
| pubmed:dateCreated |
2006-12-20
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| pubmed:abstractText |
The tumor metastasis suppressor gene Drg-1 has been shown to suppress metastasis without affecting tumorigenicity in immunodeficient mouse models of prostate and colon cancer. Expression of Drg-1 has also been found to have a significant inverse correlation with metastasis or invasiveness in various types of human cancer. However, how Drg-1 exerts its metastasis suppressor function remains unknown. In the present study, to elucidate the mechanism of action of the Drg-1 gene, we did a microarray analysis and found that induction of Drg-1 significantly inhibited the expression of activating transcription factor (ATF) 3, a member of the ATF/cyclic AMP-responsive element binding protein family of transcription factors. We also showed that Drg-1 attenuated the endogenous level of ATF3 mRNA and protein in prostate cancer cells, whereas Drg-1 small interfering RNA up-regulated the ATF3 expression. Furthermore, Drg-1 suppressed the promoter activity of the ATF3 gene, indicating that Drg-1 regulates ATF3 expression at the transcriptional level. Our immunohistochemical analysis on prostate cancer specimens revealed that nuclear expression of ATF3 was inversely correlated to Drg-1 expression and positively correlated to metastases. Consistently, we have found that ATF3 overexpression promoted invasiveness of prostate tumor cells in vitro, whereas Drg-1 suppressed the invasive ability of these cells. More importantly, overexpression of ATF3 in prostate cancer cells significantly enhanced spontaneous lung metastasis of these cells without affecting primary tumorigenicity in a severe combined immunodeficient mouse model. Taken together, our results strongly suggest that Drg-1 suppresses metastasis of prostate tumor cells, at least in part, by inhibiting the invasive ability of the cells via down-regulation of the expression of the ATF3 gene.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
|
| pubmed:issn |
0008-5472
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| pubmed:author |
pubmed-author:BandyopadhyaySucharitaS,
pubmed-author:CommesThereseT,
pubmed-author:FurutaEijiE,
pubmed-author:HaiTsonwinT,
pubmed-author:HeoYongY,
pubmed-author:HirotaShigeruS,
pubmed-author:HosobeSadahiroS,
pubmed-author:IiizumiMegumiM,
pubmed-author:LiuWenW,
pubmed-author:MiuraKunioK,
pubmed-author:MohintaSoniaS,
pubmed-author:PaiSudha KSK,
pubmed-author:PiquemalDavidD,
pubmed-author:SaitoKenK,
pubmed-author:TakanoYukioY,
pubmed-author:TsukadaTaiseiT,
pubmed-author:WangYingY,
pubmed-author:WatabeKounosukeK,
pubmed-author:WatabeMisakoM
|
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
66
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
11983-90
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| pubmed:meshHeading |
pubmed-meshheading:17178897-Activating Transcription Factor 3,
pubmed-meshheading:17178897-Cell Line, Tumor,
pubmed-meshheading:17178897-GTP-Binding Proteins,
pubmed-meshheading:17178897-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17178897-Humans,
pubmed-meshheading:17178897-Male,
pubmed-meshheading:17178897-Neoplasm Metastasis,
pubmed-meshheading:17178897-Plasmids,
pubmed-meshheading:17178897-Prostatic Neoplasms,
pubmed-meshheading:17178897-Restriction Mapping,
pubmed-meshheading:17178897-Transfection
|
| pubmed:year |
2006
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| pubmed:articleTitle |
The tumor metastasis suppressor gene Drg-1 down-regulates the expression of activating transcription factor 3 in prostate cancer.
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| pubmed:affiliation |
Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois 62794, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|