Linked Life Data

16450376

Source:http://linkedlifedata.com/resource/pubmed/id/16450376

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-4-24
pubmed:abstractText
Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. We have previously demonstrated that over-expression of ErbB2 promoted ethanol-mediated invasion of mammary epithelial cells and breast cancer cells. However, the underlying cellular/molecular mechanisms remain unknown. By gelatin zymography, we showed that over-expression of ErbB2 increased the production of matrix metalloproteinase-2 (MMP-2) and MMP-9 in human mammary epithelial cells (HB2). Transient or stable transfection of ErbB2 cDNA to HB2 cells upregulated the transcripts and the activity of the MMP-2/-9 gene promoter; the upregulation of MMP-2/-9 expression was mediated by p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (PI3K). Although ethanol, at physiologically relevant concentrations (100-400 mg/dl), did not affect the production of MMP-2/-9, it activated MMP-2 in HB2 cells over-expressing ErbB2 (HB2(ErbB2)), but not HB2 cells; it enhanced the cleavage of proform MMP-2 (72 kDa) to an active form (62 kDa). The activation was dependent on c-jun N-terminal kinases (JNKs) and reactive oxygen species (ROS). On the other hand, ethanol affected neither the expression nor the activation of MMP-9. Selective inhibitors of MMP-2 (SB-3CT and OA-Hy) and antioxidants significantly inhibited ethanol-stimulated invasion of HB2(ErbB2) cells. Furthermore, knocking down MMP-2 by small interference RNA also induced a partial blockage on ethanol-promoted invasion of HB2(ErbB2) cells. Thus, ethanol-stimulated invasion of cells over-expressing ErbB2 was mediated, at least partially, by MMP-2 activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8-16
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16450376-Blotting, Western, pubmed-meshheading:16450376-Cell Culture Techniques, pubmed-meshheading:16450376-Epithelial Cells, pubmed-meshheading:16450376-Ethanol, pubmed-meshheading:16450376-Female, pubmed-meshheading:16450376-Gene Expression Regulation, pubmed-meshheading:16450376-Genes, erbB-2, pubmed-meshheading:16450376-Humans, pubmed-meshheading:16450376-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:16450376-Mammary Glands, Human, pubmed-meshheading:16450376-Matrix Metalloproteinase 2, pubmed-meshheading:16450376-Matrix Metalloproteinase 9, pubmed-meshheading:16450376-Phosphatidylinositol 3-Kinases, pubmed-meshheading:16450376-Polymerase Chain Reaction, pubmed-meshheading:16450376-Reactive Oxygen Species, pubmed-meshheading:16450376-Receptor, erbB-2, pubmed-meshheading:16450376-Transcription, Genetic, pubmed-meshheading:16450376-Up-Regulation, pubmed-meshheading:16450376-p38 Mitogen-Activated Protein Kinases
pubmed:year
2006
pubmed:articleTitle
MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2.
pubmed:affiliation
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural