The retinoid-inducible gene I: effect on apoptosis and mitogen-activated kinase signal pathways.
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.


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.


CONCLUSIONS
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.
Huang
Shiang-Long
SL
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Shyu
Rong-Yaun
RY
Yeh
Ming-Yang
MY
Jiang
Shun-Yuan
SY
D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002455:Cell Division / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D002352:Carrier Proteins; C437968:PLAAT4 protein, human; D016271:Proto-Oncogene Proteins c-myc; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases