| Reversible immortalization of mammalian cells mediated by retroviral transfer and site-specific recombination. | |
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MedLine Citation:
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PMID: 8799138 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A procedure of reversible immortalization of primary cells was devised by retrovirus-mediated transfer of an oncogene that could be subsequently excised by site-specific recombination. This study focused on the early stages of immortalization: global induction of proliferation and life span extension of cell populations. Comparative analysis of Cre/LoxP and FLP/FRT recombination in this system indicated that only Cre/LoxP operates efficiently in primary cells. Pure populations of cells in which the oncogene is permanently excised were obtained, following differential selection of the cells. Cells reverted to their preimmortalized state, as indicated by changes in growth characteristics and p53 levels, and their fate conformed to the telomere hypothesis of replicative cell senescence. By permitting temporary and controlled expansion of primary cell populations without retaining the transferred oncogene, this strategy may facilitate gene therapy manipulations of cells unresponsive to exogenous growth factors and make practical gene targeting by homologous recombination in somatic cells. The combination of retroviral transfer and site-specific recombination should also extend gene expression studies to situations previously inaccessible to experimentation. |
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Authors:
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K A Westerman; P Leboulch |
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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, P.H.S. |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 93 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 1996 Aug |
Date Detail:
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Created Date: 1996-10-31 Completed Date: 1996-10-31 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 8971-6 Citation Subset: IM |
Affiliation:
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Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge 02139, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Animals Cattle Cell Aging Cell Line, Transformed Cell Transformation, Viral* DNA Nucleotidyltransferases Gene Transfer Techniques* Genetic Vectors Humans Integrases Kidney / cytology Mice Muscle, Smooth, Vascular / cytology Rabbits Recombination, Genetic* Simian virus 40 / genetics* Skin / cytology Telomere / metabolism Transduction, Genetic Viral Proteins* |
| Grant Support | |
ID/Acronym/Agency:
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HL48374-01/HL/NHLBI NIH HHS; HL55435-01/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Viral Proteins; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/DNA Nucleotidyltransferases; EC 2.7.7.-/FLP recombinase; EC 2.7.7.-/Integrases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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