Document Detail

Defined genetic events associated with the spontaneous in vitro transformation of ElA/Ras-expressing human IMR90 fibroblasts.
MedLine Citation:
PMID:  16280331     Owner:  NLM     Status:  MEDLINE    
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.
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:
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:
Title:  Carcinogenesis     Volume:  27     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-20     Completed Date:  2006-03-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  350-9     Citation Subset:  IM    
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
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MeSH Terms
Adenovirus E1A Proteins / physiology
Cell Culture Techniques
Cell Transformation, Neoplastic*
DNA-Binding Proteins / biosynthesis
Gene Expression Regulation
Genes, myc
Genes, ras
Genetic Predisposition to Disease
Telomerase / biosynthesis
Transduction, Genetic*
Translocation, Genetic
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Adenovirus E1A Proteins; 0/DNA-Binding Proteins; EC
Erratum In:
Carcinogenesis. 2006 Apr;27(4):882

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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