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Published on: October 16, 2017
Cancer resistance in transgenic mice expressing the SAC module of Par-4
Yanming Zhao1, Ravshan Burikhanov, Shirley Qiu
1Department of Radiation Medicine, University of Kentucky, Room 309, Combs Research Building, 800 Rose Street, Lexington, KY 40536, USA.
Abstract:
Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal/immortalized cells. The cancer-specific proapoptotic action of Par-4 is encoded in its centrally located SAC domain. We report here the characterization of a novel mouse model with ubiquitous expression of the SAC domain. Although SAC transgenic mice displayed normal development and life span, they were resistant to the growth of spontaneous, as well as oncogene-induced, autochthonous tumors. Resistance to tumorigenesis was linked to inhibition of nuclear factor-kappaB activity and induction of apoptosis by the SAC domain. Collectively, our findings provide genetic evidence that the SAC domain of Par-4 confers cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance.
Insights
The SAC domain of Prostate apoptosis response-4 (Par-4) protein prevents tumor growth in mice. This cancer-specific domain induces apoptosis and inhibits tumor development without affecting normal cell viability or lifespan.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate apoptosis response-4 (Par-4) is a tumor suppressor.
- Its cancer-specific proapoptotic function resides in the SAC domain.
- Understanding the SAC domain's role in vivo is crucial for cancer research.
Purpose of the Study:
- To characterize a novel mouse model with ubiquitous expression of the Par-4 SAC domain.
- To investigate the in vivo effects of the SAC domain on tumorigenesis and normal physiology.
- To provide genetic evidence for the SAC domain's cancer-resistance properties.
Main Methods:
- Generation of a novel transgenic mouse model expressing the SAC domain ubiquitously.
- Assessment of tumor development in spontaneous and oncogene-induced cancer models.
- Analysis of molecular mechanisms including nuclear factor-kappaB (NF-κB) activity and apoptosis induction.
Main Results:
- SAC transgenic mice exhibited normal development and lifespan.
- These mice showed significant resistance to both spontaneous and oncogene-induced tumors.
- Tumor resistance was associated with inhibited NF-κB activity and induced apoptosis by the SAC domain.
Conclusions:
- The SAC domain of Par-4 confers potent cancer resistance in a transgenic mouse model.
- This resistance is achieved without adverse effects on normal viability, aging, or lifespan.
- The findings highlight the therapeutic potential of the SAC domain in cancer treatment.
