| Cyclooxygenase-2 overexpression in MCF-10F human breast epithelial cells inhibits proliferation, apoptosis and differentiation, and causes partial transformation. | |
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MedLine Citation:
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PMID: 15856465 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To investigate the effects of cyclooxygenase-2 (COX-2) overexpression on breast cancer development, we stably transfected MCF-10F human breast epithelial cells with an expression vector containing human COX-2 cDNA oriented in the sense (10F-S) or antisense (10F-AS) direction. As expected, 10F-S cells expressed elevated levels of COX-2 protein, whereas this protein was undetectable in the 10F-AS cells. Prostaglandin E(2) production in these cells reflected COX-2 levels. The 10F-S cells had a significantly decreased rate of proliferation compared to 10F-AS or parental cells, and a delay in progression through the G(1) phase of the cell cycle. COX-2 overexpression also caused resistance to detachment-induced apoptosis (anoikis) as well as an inhibition of differentiation in cells cultured in Matrigel. Furthermore, after approximately 20 passages in culture, 10F-S cells developed fibroblast-like features, expressed vimentin, and formed foci of dense growth when cultured at confluence, suggesting that the cells were undergoing epithelial to mesenchymal transition (EMT). The 10F-S cells, however, were unable to grow in soft agar or form tumors in nude mice, suggesting that they were only partially transformed. Our observations suggest that COX-2 overexpression in human breast epithelial cells will predispose the mammary gland to carcinogenesis. |
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Authors:
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Suying Lu; Guo Yu; Yonghong Zhu; Michael C Archer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 116 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-08-03 Completed Date: 2005-10-19 Revised Date: 2007-07-24 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 847-52 Citation Subset: IM |
Affiliation:
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Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anoikis Apoptosis / physiology* Breast / cytology*, enzymology Cell Adhesion Cell Cycle Cell Differentiation / physiology* Cell Division / physiology* Cell Line Cell Transformation, Neoplastic* Cyclooxygenase 2 Dinoprostone / metabolism Epithelial Cells / cytology, enzymology* Female Genetic Vectors Humans Membrane Proteins Prostaglandin-Endoperoxide Synthases / genetics*, metabolism Recombinant Proteins / metabolism Transfection |
| Chemical | |
Reg. No./Substance:
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0/Membrane Proteins; 0/Recombinant Proteins; 363-24-6/Dinoprostone; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases |
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