Cell-type specific regulation of gene expression by simian virus 40 T antigens.
SV40 transforms cells through the action of two oncoproteins, large T antigen and small t antigen. Small t antigen targets phosphatase PP2A, while large T antigen stimulates cell proliferation and survival by action on multiple proteins, including the tumor suppressors Rb and p53. Large T antigen also binds components of the transcription initiation complex and several transcription factors. We examined global gene expression in SV40-transformed mouse embryo fibroblasts, and in enterocytes obtained from transgenic mice. SV40 transformation alters the expression of approximately 800 cellular genes in both systems. Much of this regulation is observed in both MEFs and enterocytes and is consistent with T antigen action on the Rb-E2F pathway. However, the regulation of many genes is cell-type specific, suggesting that unique signaling pathways are activated in different cell types upon transformation, and that the consequences of SV40 transformation depends on the type of cell targeted.
Cantalupo
Paul G
PG
Department of Biological Sciences, 559 Crawford Hall, University of Pittsburgh Pittsburgh, Pennsylvania 15260, USA.
Sáenz-Robles
Maria Teresa
MT
Rathi
Abhilasha V
AV
Beerman
Rebecca W
RW
Patterson
William H
WH
Whitehead
Robert H
RH
Pipas
James M
JM
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D002478:Cells, Cultured; D020895:Enterocytes / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D013539:Simian virus 40 / Q000502:physiology*
D000952:Antigens, Polyomavirus Transforming