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GW112, a novel antiapoptotic protein that promotes tumor growth
Xiuwu Zhang1, Qian Huang, Zhonghui Yang
1Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Abstract:
GW112 is a novel gene that has little homology to other known genes. It is overexpressed in a number of human tumor types, especially in those of the digestive system. We show here that GW112 is associated with GRIM-19, a protein known to be involved in regulating cellular apoptosis. Functionally, GW112 could significantly attenuate the ability of GRIM19 to mediate retinoic acid-IFN-beta-mediated cellular apoptosis and apoptosis-related gene expression. In addition, GW112 demonstrated strong antiapoptotic effects in tumor cells treated with other stress exposures such as hydrogen peroxide. Finally, forced overexpression of GW112 in murine prostate tumor cells led to more rapid tumor formation in a syngeneic host. Taken together, our data suggest that GW112 is an important regulator of cell death that plays important roles in tumor cell survival and tumor growth.
Insights
The novel gene GW112 inhibits apoptosis, promoting tumor cell survival and growth. It counteracts GRIM-19
Area of Science:
- Molecular Biology
- Oncology
- Cell Death Research
Background:
- GW112 is a novel gene with limited homology to known genes.
- GW112 is overexpressed in various human tumors, particularly digestive system cancers.
- GRIM-19 is a known regulator of cellular apoptosis.
Purpose of the Study:
- To investigate the role of GW112 in apoptosis regulation.
- To determine GW112's functional interaction with GRIM-19.
- To assess GW112's impact on tumor cell survival and growth.
Main Methods:
- Co-immunoprecipitation to study GW112 and GRIM-19 association.
- Apoptosis assays in tumor cells treated with retinoic acid, IFN-beta, and hydrogen peroxide.
- In vivo tumor formation studies using GW112-overexpressing murine prostate tumor cells.
Main Results:
- GW112 associates with GRIM-19.
- GW112 attenuates GRIM-19-mediated apoptosis induced by retinoic acid and IFN-beta.
- GW112 exhibits antiapoptotic effects against hydrogen peroxide-induced stress.
- Overexpression of GW112 accelerates tumor formation in vivo.
Conclusions:
- GW112 is a novel regulator of apoptosis.
- GW112 promotes tumor cell survival and growth by inhibiting cell death pathways.
- GW112 represents a potential therapeutic target in cancer treatment.
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