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Brg-1 mediates the constitutive and fenretinide-induced expression of SPARC in mammary carcinoma cells via its interaction with transcription factor Sp1
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| Zeitschriftentitel: | Molecular Cancer |
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| Personen und Körperschaften: | , , , , , |
| In: | Molecular Cancer, 9, 2010, 1 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Springer Science and Business Media LLC
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Secreted protein, acidic and rich in cysteine (SPARC) is a matricellular protein that mediates cell-matrix interactions. It has been shown, depending on the type of cancer, to possess either pro- or anti-tumorigenic properties. The transcriptional regulation of the SPARC gene expression has not been fully elucidated and the effects of anti-cancer drugs on this process have not been explored.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the present study, we demonstrated that chromatin remodeling factor Brg-1 is recruited to the proximal SPARC promoter region (-130/-56) through an interaction with transcription factor Sp1. We identified Brg-1 as a critical regulator for the constitutive expression levels of SPARC mRNA and protein in mammary carcinoma cell lines and for SPARC secretion into culture media. Furthermore, we found that Brg-1 cooperates with Sp1 to enhance SPARC promoter activity. Interestingly, fenretinide [N-4(hydroxyphenyl) retinamide, 4-HPR], a synthetic retinoid with anti-cancer properties, was found to up-regulate the transcription, expression and secretion of SPARC via induction of the Brg-1 in a dose-dependent manner. Finally, our results demonstrated that fenretinide-induced expression of SPARC contributes significantly to a decreased invasion of mammary carcinoma cells.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Overall, our results reveal a novel cooperative role of Brg-1 and Sp1 in mediating the constitutive and fenretinide-induced expression of SPARC, and provide new insights for the understanding of the anti-cancer effects of fenretinide.</jats:p></jats:sec> |
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| ISSN: |
1476-4598
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| DOI: | 10.1186/1476-4598-9-210 |