Evolutionary conservation of the insulinoma gene rig and its possible function
The authors have identified a gene, rig (rat insulinoma gene), that is activated in chemically induced rat insulinomas but not in normal pancreatic islets or in regenerating islets. In the present study, they have found that the insulinoma gene was activated in a BK virus-induced hamster insulinoma cell line and in a spontaneously occurring human insulinoma. From the hamster and human insulinoma cDNA libraries, rig homologues were isolated, and their nucleotide sequences were determined. In the same manner as the rat gene, both hamster and human homologues contained one open reading frame of 435 nucleotides, differing by 32- and 41-base substitutions, respectively. All the base substitutions were same-sense mutations. Accordingly, the deduced 145-amino acid sequence remained invariant in hamster, human, and rat insulinomas, suggesting that rig has evolved under extraordinarily strong selective constraints. Computerized structure analysis indicated that rig-encoded protein is a possible DNA-binding protein. The antisense oligodeoxyribonucleotide complementary to hamster rig mRNA was synthesized and injected into the hamster insulinoma cells. The antisense rig oligodeoxyribouncleotide inhibited DNA synthesis in the insulinoma cells, whereas the sense rig oligodeoxyribonucleotide or antisense insulin oligodeoxyribonucleotide had no inhibitory effect. These results strongly suggest that the activation of rig is both common and potentially significant in the oncogenic growth of pancreatic B cells of islets of Langerhans.
- Research Organization:
- Tohoku Univ. School of Medicine, Sendai (Japan)
- OSTI ID:
- 7000041
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:19
- Country of Publication:
- United States
- Language:
- English
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ONCOGENES
BIOLOGICAL EVOLUTION
DNA-CLONING
PROTEINS
AMINO ACID SEQUENCE
RECOMBINANT DNA
DNA SEQUENCING
BIOLOGICAL FUNCTIONS
ELECTROPHORESIS
HYBRIDIZATION
INSULIN
MAN
MESSENGER-RNA
METHIONINE
PANCREAS
PHOSPHORUS 32
RATS
SULFUR 35
TUMOR CELLS
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CLONING
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA
DRUGS
ENDOCRINE GLANDS
EVEN-ODD NUCLEI
FUNCTIONS
GENES
GLANDS
HORMONES
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RNA
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
SULFUR ISOTOPES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques