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Evolutionary conservation of the insulinoma gene rig and its possible function
1Department of Biochemistry, Tohoku University School of Medicine, Miyagi, Japan.
Summary
The rat insulinoma gene (rig) is activated in hamster and human insulinomas, suggesting its role in pancreatic B cell tumor growth. Inhibiting rig with antisense oligodeoxyribonucleotides suppressed insulinoma cell DNA synthesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The rat insulinoma gene (rig) is identified as activated in chemically induced rat insulinomas.
- Its role in other insulinoma models and human tumors was previously uncharacterized.
Purpose of the Study:
- To investigate the activation and functional significance of rig in hamster and human insulinomas.
- To determine the evolutionary conservation and potential function of the rig-encoded protein.
Main Methods:
- Isolation and sequencing of rig homologues from hamster and human insulinoma cDNA libraries.
- Computerized analysis of protein structure and sequence.
- Inhibition of DNA synthesis in hamster insulinoma cells using antisense rig oligodeoxyribonucleotides.
Main Results:
- Rig homologues were identified and sequenced in BK virus-induced hamster and spontaneously occurring human insulinomas.
- The deduced amino acid sequence of rig was invariant across rat, hamster, and human insulinomas, indicating strong selective pressure.
- Antisense rig oligodeoxyribonucleotides significantly inhibited DNA synthesis in hamster insulinoma cells, while control oligodeoxyribonucleotides had no effect.
Conclusions:
- Rig activation is common in insulinomas across species.
- The rig-encoded protein, a potential DNA-binding protein, plays a significant role in the oncogenic growth of pancreatic B cells.
- Targeting rig may offer a therapeutic strategy for insulinoma treatment.