Compensatory apoptosis in response to SV40 large T antigen expression in the liver.
Oncogene
; 11(12): 2583-90, 1995 Dec 21.
Article
in En
| MEDLINE
| ID: mdl-8545115
ABSTRACT
Transgenesis allows the in vivo determination of the effects of oncogene expression in normal tissues. In an attempt to understand the mechanism underlying liver transformation, we have previously created transgenic mice carrying the SV40 early gene sequences, which developed hepatocarcinoma in a reproducible way. In the present study, we show that constant expression of the transgene was directly correlated to an abnormally increased hepatocyte proliferation, even at the adult stage. We further demonstrate in this model that the preneoplastic stage of hepatocarcinoma is characterized by marked ploidy alterations as early as 1 month, including the emergence of aneuploid and hyperpolyploid cells, and the persistence of an important diploid cell population. We show that this elevated proliferation is early and transiently counterbalanced by a mechanism of apoptosis, which maintains liver homeostasis. The disappearance of this programmed cell death response effective during preneoplasia might signal the commitment of the liver to neoplasia.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Precancerous Conditions
/
Antigens, Polyomavirus Transforming
/
Apoptosis
/
Simian virus 40
/
Liver
/
Liver Neoplasms, Experimental
Limits:
Animals
Language:
En
Journal:
Oncogene
Year:
1995
Document type:
Article