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Cell-type specific regulation of gene expression by simian virus 40 T antigens
Paul G Cantalupo1, Maria Teresa Sáenz-Robles, Abhilasha V Rathi
1Department of Biological Sciences, 559 Crawford Hall, University of Pittsburgh Pittsburgh, Pennsylvania 15260, USA.
Abstract:
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.
Insights
Simian virus 40 (SV40) alters ~800 genes via large T antigen, impacting cell growth. While some effects are universal, SV40 transformation shows cell-type specific gene regulation, influencing outcomes.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- SV40 oncoproteins (large T and small t antigens) drive cellular transformation.
- Large T antigen affects cell proliferation, survival, and transcription factor binding.
- Small t antigen interacts with phosphatase PP2A.
Purpose of the Study:
- To investigate global gene expression changes induced by SV40 transformation.
- To compare SV40-driven gene expression in mouse embryo fibroblasts (MEFs) and enterocytes.
Main Methods:
- Analysis of global gene expression in SV40-transformed MEFs.
- Examination of gene expression in enterocytes from SV40 transgenic mice.
Main Results:
- SV40 transformation altered the expression of approximately 800 cellular genes in both MEFs and enterocytes.
- A significant portion of gene regulation was consistent with the Rb-E2F pathway.
- Cell-type specific gene regulation was observed, indicating unique signaling pathway activation.
Conclusions:
- SV40 transformation induces widespread gene expression changes.
- The Rb-E2F pathway is a common target of SV40 large T antigen.
- SV40's impact on gene expression and cellular outcomes is context-dependent, varying by cell type.
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