| Knockdown of p53 combined with expression of the catalytic subunit of telomerase is sufficient to immortalize primary human ovarian surface epithelial cells. | |
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MedLine Citation:
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PMID: 16829690 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ovarian cancer is developed from a single layer of thin epithelial cells covering the surface of ovary, named human ovarian surface epithelial cells. Like all primary human cells, human ovarian surface epithelial cells have a finite life span and will go into senescence and eventually die when cultured in vitro. Immortalized human ovarian surface epithelial cells will provide an important model system with which to study ovarian cancer initiation and progression. Here, we show that silencing p53 expression with retrovirus-mediated small interfering RNA can delay the senescence and extend cell passage number, but is not sufficient to immortalize normal ovarian surface epithelial cells. Introduction of the catalytic subunit of telomerase is similarly insufficient to achieve immortalization. However, concurrent disruption of p53 expression with small interfering RNA retroviral constructs and ectopic expression of the catalytic subunit of telomerase was sufficient to induce cellular immortalization in 3 of 3 human ovarian surface epithelial cell cultures tested. The immortalization is associated with increased telomerase activity and telomere length, and attenuated response of cell-cycle regulatory proteins to irradiation. The resultant immortal cells continued to express the same specific cytokeratins 8 and 18 as parental cells did, indicating that the epithelial characters are still maintained in the immortal cells. In addition, the immortalized cells are non-tumorigenic and nearly diploid, which is in constrast with one immortalized by SV40 T/t antigens and hTERT. As both p53 pathway dysfunction and activation of telomerase are commonly present in human ovarian cancer, these immortal cells provide an authetic cell model system for the study of the human ovarian cancer initiation, progression, differentiation and chemoprevention. |
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Authors:
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Gong Yang; Daniel G Rosen; Imelda Mercado-Uribe; Justin A Colacino; Gordon B Mills; Robert C Bast; Chenyi Zhou; Jinsong Liu |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-07-08 |
Journal Detail:
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Title: Carcinogenesis Volume: 28 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2006-12-14 Completed Date: 2007-02-08 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 174-82 Citation Subset: IM |
Affiliation:
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Department of Pathology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, Polyomavirus Transforming / genetics, metabolism Blotting, Western Catalytic Domain* Cell Aging Cell Differentiation Cell Line, Transformed* Cell Transformation, Neoplastic Epithelial Cells / cytology, physiology Female Genetic Vectors Humans Immunoenzyme Techniques Karyotyping Keratin-8 / metabolism Mice Mice, Inbred BALB C Mice, Nude Ovary / cytology*, metabolism Telomerase / genetics, metabolism* Telomere / metabolism Tumor Suppressor Protein p53 / antagonists & inhibitors, genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA016672/CA/NCI NIH HHS; IP50CA83638/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Polyomavirus Transforming; 0/Keratin-8; 0/Tumor Suppressor Protein p53; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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