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The retinoid-inducible gene I: effect on apoptosis and mitogen-activated kinase signal pathways
Shiang-Long Huang1, Rong-Yaun Shyu, Ming-Yang Yeh
1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Background:
The retinoid-inducible gene I (RIG1), belonging to the family of type II tumor suppressor genes, was isolated from human gastric cancer cells treated with all-trans retinoic acid. The activity of the RIG1 gene was investigated in this study.
Materials And Methods:
HtTA cervical and TSGH9201 gastric cancer cells were transiently transfected with expression vectors that synthesized RIG1-myc or RIG1-EGFP fusion protein. Cell growth was analyzed by measuring the incorporation of bromodeoxyuridine. Apoptosis was evaluated by the formation of in situ DNA breakage. The activities of mitogen-activated kinase signal pathways were analyzed using signal pathway trans-reporting systems.
Results:
Expression of the RIG1-myc fusion protein resulted in decreased cell growth. Both RIG1-EGFP and RIG1-myc fusion proteins induced cellular apoptosis that was characterized by the presence of apoptotic bodies and in situ DNA breakage. The transactivation activities of Elk1, c-Jun and CHOP proteins were suppressed by 80, 50 and 88%, respectively, in HtTA cells expressing the RIG1-myc fusion protein for two days. Similarly, the transactivation activities of the CHOP protein was suppressed in TSGH9201 and HtTA cells transiently expressing RIG1-myc and RIG1-EGFP, respectively.
Conclusion:
The RIG1 fusion proteins exhibited growth suppressive and apoptosis-inducing activity. The protein negatively-regulated signal pathways of extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 mitogen-activated kinase.
Insights
Retinoid-inducible gene I (RIG1) fusion proteins demonstrated significant tumor suppressor activity by inhibiting cancer cell growth and inducing apoptosis. RIG1 negatively impacts key mitogen-activated protein kinase pathways, offering potential therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Retinoid-inducible gene I (RIG1) is a type II tumor suppressor gene.
- RIG1 was identified in human gastric cancer cells following all-trans retinoic acid treatment.
- This study investigates the functional activity of the RIG1 gene.
Purpose of the Study:
- To analyze the impact of RIG1 fusion proteins on cancer cell proliferation.
- To evaluate the apoptosis-inducing potential of RIG1.
- To determine RIG1's effect on mitogen-activated protein kinase (MAPK) signaling pathways.
Main Methods:
- Cancer cell lines (HtTA and TSGH9201) were transfected with RIG1-myc or RIG1-EGFP expression vectors.
- Cell growth was quantified using bromodeoxyuridine incorporation.
- Apoptosis was assessed via in situ DNA breakage and apoptotic body formation.
- MAPK pathway activity was measured using trans-reporting systems.
Main Results:
- RIG1-myc expression led to reduced cancer cell growth.
- Both RIG1-EGFP and RIG1-myc induced apoptosis, evidenced by apoptotic bodies and DNA fragmentation.
- RIG1 suppressed the transactivation activity of Elk1, c-Jun, and CHOP proteins by 80%, 50%, and 88%, respectively.
- CHOP protein activity was also suppressed in both cell lines expressing RIG1 fusion proteins.
Conclusions:
- RIG1 fusion proteins exhibit potent growth-suppressive and apoptosis-inducing effects on cancer cells.
- RIG1 negatively regulates critical MAPK pathways, including ERK, JNK, and p38.
- These findings highlight RIG1's role as a tumor suppressor and its potential therapeutic implications.