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, p38alpha 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 p38alpha in breast cancer bone metastases, using dominant negative blockade approach. Human MDA-MB-231 breast cancer clones stably expressing dominant negative p38alpha (p38/AF) exhibited decreased basal MMP-9 activity. TGF-beta1-induced MMP-9 activity was also blunted in these clones, as compared with controls in which TGF-betal up-regulated MMP-9 activity. Consistent with these findings, SB202190, a specific p38 inhibitor, also inhibited TGF-beta1-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 p38alpha 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.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Suarez-Cuervo C,Merrell MA,Watson L,Harris KW,Rosenthal EL,Väänänen HK,Selander KSdoi
10.1007/s10585-004-3503-xsubject
Has Abstractpub_date
2004-01-01 00:00:00pages
525-33issue
6eissn
0262-0898issn
1573-7276journal_volume
21pub_type
杂志文章abstract：:Previous studies from our laboratory have demonstrated that metastatic propensity is significantly influenced by the genetic background upon which tumors arise. We have also established that human gene expression profiles predictive of metastasis are not only present in mouse tumors with both high and low metastatic c...
journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1023/a:1018400826845
更新日期：1997-03-01 00:00:00
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journal_title：Clinical & experimental metastasis
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更新日期：2009-01-01 00:00:00
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1023/a:1006649617918
更新日期：1999-01-01 00:00:00
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journal_title：Clinical & experimental metastasis
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更新日期：2010-01-01 00:00:00
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journal_title：Clinical & experimental metastasis
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
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doi：10.1007/s10585-005-3098-x
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章,评审
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更新日期：2018-04-01 00:00:00
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
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更新日期：2019-08-01 00:00:00
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journal_title：Clinical & experimental metastasis
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更新日期：2012-06-01 00:00:00
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/BF01784377
更新日期：1988-11-01 00:00:00
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/BF01753837
更新日期：1994-07-01 00:00:00
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
doi：10.1007/BF00115110
更新日期：1996-11-01 00:00:00
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journal_title：Clinical & experimental metastasis
pub_type： 杂志文章
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更新日期：1991-03-01 00:00:00
abstract：:Smad interacting protein 1 (SIP1) is an epithelial-mesenchymal transition (EMT)-inducible gene that plays a key role in tumor progression in various cancers. This study seeks to clarify the clinical and biological significance of SIP1 expression, especially in intestinal type gastric cancer. We analyzed the mRNA level...
journal_title：Clinical & experimental metastasis
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doi：10.1007/s10585-012-9547-4
更新日期：2013-04-01 00:00:00
