| Efficient immortalization of primary human cells by p16INK4a-specific short hairpin RNA or Bmi-1, combined with introduction of hTERT. | |
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MedLine Citation:
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PMID: 17233832 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation of telomerase is sufficient for immortalization of some types of human cells but additional factors may also be essential. It has been proposed that stress imposed by inadequate culture conditions induces senescence due to accumulation of p16(INK4a). Here, we present evidence that many human cell types undergo senescence by activation of the p16(INK4a)/Rb pathway, and that introduction of Bmi-1 can inhibit p16(INK4a) expression and extend the life span of human epithelial cells derived from skin, mammary gland and lung. Introduction of p16(INK4a)-specific short hairpin RNA, as well as Bmi-1, suppressed p16(INK4a) expression in human mammary epithelial cells without promoter methylation, and extended their life span. Subsequent introduction of hTERT, the telomerase catalytic subunit, into cells with low p16(INK4a) levels resulted in efficient immortalization of three cell types without crisis or growth arrest. The majority of the human mammary epithelial cells thus immortalized showed almost normal ploidy as judged by G-banding and spectral karyotyping analysis. Our data suggest that inhibition of p16(INK4a) and introduction of hTERT can immortalize many human cell types with little chromosomal instability. |
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Authors:
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Kei Haga; Shin-ichi Ohno; Takashi Yugawa; Mako Narisawa-Saito; Masatoshi Fujita; Michiie Sakamoto; Denise A Galloway; Tohru Kiyono |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer science Volume: 98 ISSN: 1347-9032 ISO Abbreviation: Cancer Sci. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-01-19 Completed Date: 2007-02-23 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: England |
Other Details:
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Languages: eng Pagination: 147-54 Citation Subset: IM |
Affiliation:
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Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuoku 104-0045, Tokyo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Catalysis Cell Aging Cell Proliferation Cells, Cultured Cyclin-Dependent Kinase Inhibitor p16 / genetics*, metabolism* DNA Methylation Down-Regulation Enzyme Activation Epithelial Cells / cytology, metabolism Humans Karyotyping Keratinocytes / metabolism Nuclear Proteins / genetics*, metabolism* Promoter Regions, Genetic / genetics Proto-Oncogene Proteins / genetics*, metabolism* RNA Interference Repressor Proteins / genetics*, metabolism* Telomerase / genetics, metabolism* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p16; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Repressor Proteins; 138791-04-5/BMI1 protein, human; EC 2.7.7.49/Telomerase |
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