Carcinogenesis Advance Access originally published online on November 9, 2005
Carcinogenesis 2006 27(2):350-359; doi:10.1093/carcin/bgi264
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis Vol.27 no.2 © Oxford University Press 2005; all rights reserved.
ARTICLES |
Defined genetic events associated with the spontaneous in vitro transformation of ElA/Ras-expressing human IMR90 fibroblasts
1 Department of Pharmacology and Therapeutics and 2 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA, 3 Department of Cellular Biology and Anatomy, 4 Department of Pathology and 5 Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA and 6 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
7 Present address: ZeptoMetrix Corporation, 872 Main Street, Buffalo, NY 14202, USA
8 Present address: FasterCures, The Center for Accelerating Medical Solutions, 509 7th Street, Washington, DC 20004, USA
* To whom correspondence should be addressed. Tel: +1 716 845 1548; Fax: +1 716 845 8857; E-mail: Athena.Lin{at}roswellpark.org.
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. L. Callejas-Valera, J. Guinea-Viniegra, C. Ramirez-Castillejo, J. A. Recio, E. Galan-Moya, N. Martinez, J. M. Rojas, S. R. y Cajal, and R. Sanchez-Prieto E1a Gene Expression Blocks the ERK1/2 Signaling Pathway by Promoting Nuclear Localization and MKP Up-regulation: IMPLICATION IN v-H-Ras-INDUCED SENESCENCE J. Biol. Chem., May 9, 2008; 283(19): 13450 - 13458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Mahale, Z. A.T. Khan, M. Igarashi, G. J. Nanjangud, R. F. Qiao, S. Yao, S. W. Lee, and S. A. Aaronson Clonal Selection in Malignant Transformation of Human Fibroblasts Transduced with Defined Cellular Oncogenes Cancer Res., March 1, 2008; 68(5): 1417 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Culver and S. M. Laster Adenovirus Type 5 Exerts Multiple Effects on the Expression and Activity of Cytosolic Phospholipase A2, Cyclooxygenase-2, and Prostaglandin Synthesis J. Immunol., September 15, 2007; 179(6): 4170 - 4179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, A. W. Lin, X. Zhang, Y. Wang, X. Wang, and D. W. Goodrich Cancer Cells and Normal Cells Differ in Their Requirements for Thoc1 Cancer Res., July 15, 2007; 67(14): 6657 - 6664. [Abstract] [Full Text] [PDF]
|
|