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Published on: June 9, 2017
Identification of specific PP2A complexes involved in human cell transformation
Wen Chen1, Richard Possemato, K Thirza Campbell
1Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Abstract:
The SV40 small t antigen (ST) interacts with the serine-threonine protein phosphatase 2A (PP2A). To investigate the role of this interaction in transformation, we suppressed the expression of the PP2A B56gamma subunit in human embryonic kidney (HEK) epithelial cells expressing SV40 large T antigen, hTERT, and H-RAS. Suppression of PP2A B56gamma expression inhibited PP2A-specific phosphatase activity similar to that achieved by ST and conferred the ability to grow in an anchorage-independent fashion and to form tumors. Overexpression of PP2A B56gamma3 in tumorigenic HEK cells expressing ST or human lung cancer cell lines partially reversed the tumorigenicity of these cells. These observations identify specific PP2A complexes involved in human cell transformation.
Insights
The SV40 small t antigen interacts with protein phosphatase 2A (PP2A). Suppressing a PP2A subunit inhibited phosphatase activity, promoting cell transformation and tumor formation, revealing PP2A
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- The simian virus 40 (SV40) small t antigen (ST) is known to interact with serine-threonine protein phosphatase 2A (PP2A). This interaction is implicated in cellular transformation processes.
- Understanding the specific PP2A subunits involved in SV40-mediated transformation is crucial for deciphering cancer development mechanisms.
Purpose of the Study:
- To investigate the role of the PP2A B56gamma subunit in SV40-induced cellular transformation.
- To determine if modulating PP2A B56gamma activity can affect the tumorigenic potential of cells expressing SV40 antigens.
Main Methods:
- Suppression of the PP2A B56gamma subunit in human embryonic kidney (HEK) cells engineered to express SV40 large T antigen, hTERT, and H-RAS.
- Assessing PP2A-specific phosphatase activity following B56gamma subunit suppression.
- Evaluating anchorage-independent growth and tumor formation capabilities in modified HEK cells.
- Overexpressing the PP2A B56gamma3 subunit in tumorigenic cells and human lung cancer cell lines.
Main Results:
- Suppression of PP2A B56gamma inhibited PP2A-specific phosphatase activity, mimicking the effect of SV40 ST.
- Reduced B56gamma expression conferred anchorage-independent growth and tumor-forming abilities to the engineered HEK cells.
- Overexpression of PP2A B56gamma3 partially reversed tumorigenicity in established cancer cells.
Conclusions:
- Specific PP2A complexes, particularly those involving the B56gamma subunit, play a critical role in human cell transformation.
- Targeting PP2A B56gamma activity represents a potential therapeutic strategy for cancers associated with SV40 or similar oncogenic pathways.
