Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (23)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Ray, F.A.
Right arrow Articles by Kraemer, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ray, F.A.
Right arrow Articles by Kraemer, P. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1993 Oxford University Press

research-article

Iterative chromosome mutation and selection as a mechanism of complete transformation of human diploid fibroblasts by SV40 T antigen

F.Andrew Ray and Paul M. Kraemer

Life Sciences Division, Los Alamos National Laboratory MS M888, Los Alamos, NM 87545, USA

The acquisition of an extended lifespan and of neoplastic properties, including anchorage independence, ability to grow in low serum-containing media, morphological transformation, immortalization and tumorigenicity in nude mice were studied in 31 human fibroblast lineages transfected with plasmids containing the SV40 early genes. Plasmids were used that contained sequences for large T alone, or large T plus small t or large T plus small t plus the SV40 origin. Cells expressing large T antigen gradually acquired the ability to form colonies in low serum or to form anchorage-independent colonies. Large T antigen was sufficient to cause complete transformation to tumorigenicity if multi-step lineage evolution was obtained by prolonged serial passage and if in vivo progression was assisted by means of a gelatin sponge implantation technique. Cells derived from progressive tumors initiated in sponges showed enhanced tumorigenicity as measured by ability to obtain tumors without using sponges and with reduced latent period, higher incidence and with fewer cells inoculated. Multiple lineages of human fibroblasts have been converted to tumorigenicity without additional treatments such as transfection with activated oncogenes or exposure to carcinogens. These data, taken in conjunction with earlier studies showing that T antigen causes chromosome mutation preceding and accompanying the accumulation of the neoplastic phenotype, suggests that the T protein drives the transformation process by acting as a mutagen and cells with growth advantages were selected for in vitro and in vivo. With the possible exception of morphological transformation, the presence or absence of genes for small t and the SV40 origin were not critical for the process.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
K. Felix, A. Polack, W. Pretsch, S. H. Jackson, L. Feigenbaum, G.-W. Bornkamm, and S. Janz
Moderate Hypermutability of a Transgenic lacZ Reporter Gene in Myc-Dependent Inflammation-Induced Plasma Cell Tumors in Mice
Cancer Res., January 15, 2004; 64(2): 530 - 537.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. O. Major and J. V. Neel
The JC and BK human polyoma viruses appear to be recent introductions to some South American Indian tribes: There is no serological evidence of cross-reactivity with the simian polyoma virus SV40
PNAS, December 22, 1998; 95(26): 15525 - 15530.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Vogt, R. L. Rice, C. E. Settineri, F. Yokokawa, S. Yokokawa, P. Wipf, and J. S. Lazo
Disruption of Insulin-Like Growth Factor-1 Signaling and Down-Regulation of Cdc2 by SC-alpha alpha delta 9, a Novel Small Molecule Antisignaling Agent Identified in a Targeted Array Library
J. Pharmacol. Exp. Ther., November 1, 1998; 287(2): 806 - 813.
[Abstract] [Full Text]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.