| Profilin-1 overexpression inhibits proliferation of MDA-MB-231 breast cancer cells partly through p27kip1 upregulation. | |
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MedLine Citation:
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PMID: 20143334 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Profilin-1 (Pfn1), a ubiquitously expressed actin-binding protein, has gained interest in epithelial-derived cancer because of its downregulation in expression in various adenocarcinoma. Pfn1 overexpression impairs tumorigenic ability of human breast cancer xenografts thus suggesting that Pfn1 could be a tumor-suppressor protein. The objective of the present study was to determine how Pfn1 overexpression affects cell-cycle progression of breast cancer cells. We show that Pfn1 overexpression in MDA-MB-231 breast cancer cells causes cell-cycle arrest in G1 phase and dramatically reduced proliferation in culture. Pfn1 overexpression results in increased protein stability of p27(kip1) (p27-a major cyclin-dependent kinase inhibitor) and marked elevation in the overall cellular level of p27. Proliferation defect of Pfn1 overexpressers can be partly rescued by silencing p27 expression thus suggesting a critical role of p27 in Pfn1-induced growth inhibition of MDA-MB-231 cells. Finally, Pfn1 overexpression was found to sensitize MDA-MB-231 cells to apoptosis in response to cytotoxic stimulus thus suggesting for the first time that survival of breast cancer cells can also be negatively influenced by Pfn1 upregulation. These findings may provide novel insights underlying Pfn1's tumor-suppressive action. |
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Authors:
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Li Zou; Zhijie Ding; Partha Roy |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of cellular physiology Volume: 223 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-07 Completed Date: 2010-04-21 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 623-9 Citation Subset: IM |
Copyright Information:
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(c) 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Breast Neoplasms / genetics, pathology* Cell Line, Tumor Cell Proliferation Cell Survival Cyclin-Dependent Kinase Inhibitor p27 / genetics*, metabolism Female G1 Phase Gene Expression Regulation, Neoplastic* Humans Profilins / metabolism* Protein Stability Up-Regulation / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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CA108607/CA/NCI NIH HHS; R01 CA108607-04/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Profilins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27 |
| Comments/Corrections | |
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