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Breast cancer cells with inhibition of p38 α have decreased MMP-9 activity and exhibit decreased bone metastasis in mice.
- Source :
- Clinical & Experimental Metastasis; Nov2004, Vol. 21 Issue 6, p525-533, 9p
- Publication Year :
- 2004
-
Abstract
- p38 belongs to a family of mitogen-activated protein kinases, which transfer extracellular signals into intracellular responses. p38 is also frequently detected in clinical breast cancer specimens, but its role as a prognostic factor is not known. Of the various p38 isoforms, p38 β has been shown to mediate the in vitro invasiveness of breast cancer cells through up-regulation of urokinase plasminogen activator (uPA). We studied the role of p38 β in breast cancer bone metastases, using dominant negative blockade approach. Human MDA-MB-231 breast cancer clones stably expressing dominant negative p38 β (p38/AF) exhibited decreased basal MMP-9 activity. TGF- β <subscript>1</subscript>-induced MMP-9 activity was also blunted in these clones, as compared with controls in which TGF- β <subscript>1</subscript> up-regulated MMP-9 activity. Consistent with these findings, SB202190, a specific p38 inhibitor, also inhibited TGF-β<subscript>1</subscript>-induced MMP-9 activity in parental cells. The p38/AF clones exhibited also reduced uPA production after growth on vitronectin and decreased cell motility, as compared with controls. VEGF production levels in all the studied clones were similar. The p38/AF clone, which had similar in vitro growth rate as the control pcDNA3 clone, formed significantly less bone metastases in a mouse model, as compared with the control clone. In conclusion, inhibition of the p38 β pathway results in decreased MMP-9 activity, impaired uPA expression and decreased motility, all of which may contribute to the decreased formation of bone metastasis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02620898
- Volume :
- 21
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Metastasis
- Publication Type :
- Academic Journal
- Accession number :
- 51583530
- Full Text :
- https://doi.org/10.1007/s10585-004-3503-x