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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-2-26
pubmed:abstractText
The tumor suppressor PTEN is one of the most commonly inactivated genes in human cancer. PTEN, an inositol phosphatase specific for the products of PI 3-kinase, is known to inhibit PDGF-mediated vascular smooth muscle cell (VSMC) proliferation and migration. However, little is known about the molecular mechanisms by which this tumor suppressor regulates cell growth and migration in VSMC. Here, we show that PTEN expression has the potent inhibitory effect on DNA synthesis of cultured VSMC in the presence of PDGF. The growth suppression of PTEN was mediated by its ability to block cell cycle progression in the G1 phase. Such an arrest correlated with down-regulation of cyclins and CDKs and up-regulation of the CDK inhibitor p21 and p27 expression, whereas up-regulation of p53 by PTEN expression was not observed. Expression of PTEN also led to the inhibition of TNF-alpha-induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, PTEN expression strongly decreased MMP-9 promoter activity in response to TNF-alpha. This inhibition was characterized by down-regulation of MMP-9, which was transcriptionally regulated at NF-kappaB and activation protein-1 (AP-1) sites in the MMP-9 promoter. These findings indicate the efficacy of PTEN in inhibiting cell proliferation, G1-S phase cell cycle progress, and MMP-9 expression through the transcription factors NF-kappaB and AP-1 in VSMC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
421
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-76
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
PTEN induces G1 cell cycle arrest and inhibits MMP-9 expression via the regulation of NF-kappaB and AP-1 in vascular smooth muscle cells.
pubmed:affiliation
National Research Laboratory for Glycobiology, Korean Ministry of Science and Technology, Kyungju, Kyungbuk 780-714, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't