Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
34
|
| pubmed:dateCreated |
1997-9-15
|
| pubmed:abstractText |
The cyclooxygenase (Cox) enzyme catalyzes the rate-limiting oxidative and peroxidative enzymatic steps in the biosynthesis of prostanoids. Both Cox-1 and -2 genes encode the two isoenzymes that carry out similar enzymatic steps. Enhanced Cox activity is associated with proliferative diseases such as colon cancer. To determine if a cause and effect relationship exists between Cox isoenzyme overexpression and tumorigenesis, the human Cox-1 and Cox-2 isoenzymes were transfected into ECV immortalized endothelial cells. Although numerous clones of Cox-1 expressing cells were obtained, Cox-2 overexpression resulted in growth disadvantage and increased cell death. In contrast, Cox-1 overexpressing cells expressed high levels of the functional Cox-1 polypeptide in the endoplasmic reticulum and the nucleus. In vitro proliferation of these cells was reduced compared with vector-transfected ECV cells. Cox-1 overexpression also enhanced the tumor necrosis factor-alpha-induced apoptosis of ECV cells 2-fold. In contrast to the in vitro behavior, ECV-Cox-1 cells proliferated aggressively and formed tumors in athymic "nude" mice, whereas the vector-transfected counterparts did not. The growth of Cox-1-induced tumors was not inhibited by indomethacin, suggesting a nonprostanoid function of Cox-1. ECV-Cox-1-derived tumors were angiosarcoma-like and contained numerous host-derived neovessels. These data suggest that Cox-1 overexpression in immortalized ECV endothelial cells results in nuclear localization of the polypeptide and tumorigenesis.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptgs1 protein, mouse
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
22
|
| pubmed:volume |
272
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
21455-60
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9261162-Animals,
pubmed-meshheading:9261162-Apoptosis,
pubmed-meshheading:9261162-Cell Division,
pubmed-meshheading:9261162-Cell Transformation, Neoplastic,
pubmed-meshheading:9261162-Cyclooxygenase 1,
pubmed-meshheading:9261162-Cyclooxygenase 2,
pubmed-meshheading:9261162-Endothelium, Vascular,
pubmed-meshheading:9261162-Humans,
pubmed-meshheading:9261162-Isoenzymes,
pubmed-meshheading:9261162-Membrane Proteins,
pubmed-meshheading:9261162-Mice,
pubmed-meshheading:9261162-Mice, Nude,
pubmed-meshheading:9261162-Neoplasm Transplantation,
pubmed-meshheading:9261162-Neoplasms, Experimental,
pubmed-meshheading:9261162-Neovascularization, Pathologic,
pubmed-meshheading:9261162-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:9261162-Transfection,
pubmed-meshheading:9261162-Transplantation, Heterologous
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Tumorigenic transformation of immortalized ECV endothelial cells by cyclooxygenase-1 overexpression.
|
| pubmed:affiliation |
Department of Clinical Chemistry and Obstetrics and Gynecology, Haartman Institute, Helsinki University, Helsinki, Finland.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|