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Science 6 September 1996:
Vol. 273. no. 5280, pp. 1384 - 1386
DOI: 10.1126/science.273.5280.1384
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Reports

Time-Sensitive Reversal of Hyperplasia in Transgenic Mice Expressing SV40 T Antigen

Dagmar Ewald, Minglin Li, Shimon Efrat, Gert Auer, Robert J. Wall, Priscilla A. Furth, * Lothar Hennighausen *

The role of viral oncoprotein expression in the maintenance of cellular transformation was examined as a function of time through controlled expression of simian virus 40 T antigen (TAg). Expression of TAg in the submandibular gland of transgenic mice from the time of birth induced cellular transformation and extensive ductal hyperplasia by 4 months of age. The hyperplasia was reversed when TAg expression was silenced for 3 weeks. When TAg expression was silenced after 7 months, however, the hyperplasia persisted even though TAg was absent. Although the polyploidy of ductal cells could be reversed at 4 months of age, cells at 7 months of age remained polyploid even in the absence of TAg. These results support a model of time-dependent multistep tumorigenesis, in which virally transformed cells eventually lose their dependence on the viral oncoprotein for maintenance of the transformed state.

D. Ewald and L. Hennighausen, Laboratory of Biochemistry and Metabolism, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
M. Li and P. A. Furth, Division of Infectious Diseases, Department of Medicine, University of Maryland Medical School and the Institute of Human Virology, Baltimore, MD 21201, USA.
S. Efrat, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
G. Auer, Department of Oncology and Pathology, Karolinska Institute, S-17176 Stockholm, Sweden.
R. J. Wall, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA.
*   To whom correspondence should be addressed at furth{at}ncifcrf.gov (for P. A. Furth) or hennighausen{at}nih.gov (for L. Hennighausen).


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