Document Detail


Cyclooxygenase-2 overexpression in MCF-10F human breast epithelial cells inhibits proliferation, apoptosis and differentiation, and causes partial transformation.
MedLine Citation:
PMID:  15856465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Suying Lu; Guo Yu; Yonghong Zhu; Michael C Archer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2005-08-03     Completed Date:  2005-10-19     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  847-52     Citation Subset:  IM    
Affiliation:
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
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MeSH Terms
Descriptor/Qualifier:
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:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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