Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen.
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.
Ewald
D
D
Laboratory of Biochemistry and Metabolism, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Li
M
M
Efrat
S
S
Auer
G
G
Wall
R J
RJ
Furth
P A
PA
Hennighausen
L
L
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D015870:Gene Expression; D006965:Hyperplasia; D051379:Mice; D008822:Mice, Transgenic; D011123:Polyploidy; D013363:Submandibular Gland / Q000473:pathology*; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D015534:Trans-Activators; D013752:Tetracycline