| Overexpression of both TFPIα and TFPIβ induces apoptosis and expression of genes involved in the death receptor pathway in breast cancer cells. | |
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MedLine Citation:
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PMID: 20886581 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thrombosis is a major complication and an important cause of death in cancer patients. Tumor cells may trigger coagulation and induce a prothrombotic phenotype, which in return may enhance angiogenesis, tumor growth, and metastasis. Tissue factor pathway inhibitor (TFPI) has been reported to reduce tumor growth and metastasis in vivo and to induce apoptosis and inhibit proliferation in normal cells in vitro. However, no effect has so far been observed in cancer cells. We therefore aimed to characterize the functional effects of ectopic overexpression and endogenous downregulation of TFPI in cancer cells, and to elucidate possible mechanisms involved. The tumor derived breast cancer cells SK-BR-3 and Sum102 were used to construct stable cell lines overexpressing TFPIα and TFPIβ, and with TFPI knocked down, respectively. Effects of altered TFPI expression were evaluated by measuring apoptosis and proliferation of the cells, and gene expressions were analyzed using PCR arrays. Increased DNA fragmentation and Caspase 3 activity was observed in SK-BR-3 cells overexpressing TFPIα and TFPIβ, while a decrease in apoptosis was seen in Sum102 cells with TFPI expression knocked down. An increase and reduction in expression of pro- and anti-apoptotic genes, respectively, were seen in TFPI overexpressing cells, and the majority of the upregulated genes encoded proteins involved in the death receptor pathway, among them the death receptor ligand TNF-α. In conclusion, TFPIα and TFPIβ induced apoptosis in breast cancer cells and increased expression of apoptotic genes indicating a possible involvement of the death receptor pathway. |
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Authors:
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Benedicte Stavik; Grethe Skretting; Marit Sletten; Per Morten Sandset; Nina Iversen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular carcinogenesis Volume: 49 ISSN: 1098-2744 ISO Abbreviation: Mol. Carcinog. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-19 Completed Date: 2010-11-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8811105 Medline TA: Mol Carcinog Country: United States |
Other Details:
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Languages: eng Pagination: 951-63 Citation Subset: IM |
Copyright Information:
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© 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Medical Genetics, Oslo University Hospital, Norway. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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genetics,
metabolism,
pathology* Apoptosis* Blotting, Western Breast Neoplasms / genetics, metabolism, pathology* Cell Proliferation Female Gene Expression Profiling* Humans Lipoproteins / antagonists & inhibitors, genetics, metabolism* RNA, Messenger / genetics RNA, Small Interfering / pharmacology Receptors, Death Domain / genetics*, metabolism Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Tumor Markers, Biological / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Lipoproteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Receptors, Death Domain; 0/Tumor Markers, Biological; 0/lipoprotein-associated coagulation inhibitor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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