| Defined genetic events associated with the spontaneous in vitro transformation of ElA/Ras-expressing human IMR90 fibroblasts. | |
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MedLine Citation:
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PMID: 16280331 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In contrast to rodent cells, normal human fibroblasts are generally resistant to neoplastic transformation in vitro. Here, we report the derivation and characterization of a spontaneously transformed cell line from normal human IMR90 fibroblasts transduced with E1A and Ras oncogenes. Unlike the parental, non-tumorigenic E1A/Ras-expressing IMR90 cells, these spontaneously transformed cells displayed aberrant growth potential in vitro and were capable of tumorigenesis in vivo. In contrast to the parental E1A/Ras-expressing cells, both the spontaneously transformed cells and cells derived from resultant tumors displayed specific t(7q;8q) and t(5q;17) structural chromosomal changes. Chromosome 8q contains c-Myc, which is capable of activating the telomerase catalytic subunit hTERT. Notably, upregulation of c-Myc, hTERT and telomerase activity were detected only in the tumorigenic cells. Transduction of Myc siRNA into the tumorigenic cells led to a concomitant downregulation of hTERT. Furthermore, transduction of Myc or hTERT into the non-tumorigenic E1A/Ras-expressing IMR90 cells was able to confer tumorigenesis on these cells. These studies suggest that the t(7;8) translocation may result in Myc overexpression and its subsequent activation of hTERT, which may contribute to the tumorigenicity of the IMR90 cells. Furthermore, this report describes additional successful neoplastic transformation of human IMR90 fibroblasts by defined genetic elements. The spontaneously transformed cells we have derived provide a valuable model system for the study of neoplastic transformation. |
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Authors:
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Douglas X Mason; Daniel Keppler; Jun Zhang; Tonya J Jackson; Yvette R Seger; Seiichi Matsui; Fleurette Abreo; John K Cowell; Gregory J Hannon; Scott W Lowe; Athena W Lin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2005-11-09 |
Journal Detail:
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Title: Carcinogenesis Volume: 27 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-20 Completed Date: 2006-03-09 Revised Date: 2007-11-14 |
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: 350-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenovirus E1A Proteins
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physiology Cell Culture Techniques Cell Transformation, Neoplastic* DNA-Binding Proteins / biosynthesis Fibroblasts* Gene Expression Regulation Genes, myc Genes, ras Genetic Predisposition to Disease Humans Telomerase / biosynthesis Transduction, Genetic* Translocation, Genetic Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA16056/CA/NCI NIH HHS; R21 CA9124785/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adenovirus E1A Proteins; 0/DNA-Binding Proteins; EC 2.7.7.49/Telomerase |
| Comments/Corrections | |
Erratum In:
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Carcinogenesis. 2006 Apr;27(4):882 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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