| Deregulation of the cell cycle by breast tumor kinase (Brk). | |
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MedLine Citation:
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PMID: 20162673 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Brk is a cytoplasmic nonreceptor tyrosine kinase that is overexpressed in breast tumors but undetectable in normal or benign mammary tissues. Brk promotes proliferation of human mammary epithelial cells and tumor growth in a mouse model, but the role of Brk in cell cycle regulation is not known. In this study, we describe the mechanism of Brk-induced deregulation of the cell cycle. We provide evidence that Brk antagonizes the transcriptional activity of the transcription factor FoxO family of proteins by inhibiting its nuclear localization. As a result, the cell cycle inhibitor p27, a FoxO target gene, is down-regulated. This event is accompanied by G1/S cell cycle progression of quiescent cells. As p27 is a key regulator of the G1/S cell cycle checkpoint, these data suggest that perturbation of p27 expression induced by Brk causes S phase entrance. Deregulation of the cell cycle is a key event in neoplasia, and thus, the mechanism presented here likely contributes to breast cancer development. |
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Authors:
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Edward Chan; Anjaruwee S Nimnual |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 127 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-09-29 Completed Date: 2010-11-04 Revised Date: 2011-12-26 |
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: 2723-31 Citation Subset: IM |
Affiliation:
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Department of Pediatric Hematology/Oncology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Breast Neoplasms
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enzymology*,
genetics,
pathology* Cell Cycle / physiology* Cell Growth Processes / physiology Cell Line, Tumor Cell Nucleus / metabolism Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis, metabolism Down-Regulation Female Forkhead Transcription Factors / antagonists & inhibitors, genetics, metabolism G1 Phase / physiology Humans Neoplasm Proteins / genetics, metabolism* Protein-Tyrosine Kinases / genetics, metabolism* RNA, Small Interfering / administration & dosage, genetics S Phase / physiology Transfection |
| Chemical | |
Reg. No./Substance:
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0/FOXO3 protein, human; 0/Forkhead Transcription Factors; 0/Neoplasm Proteins; 0/RNA, Small Interfering; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/PTK6 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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