Insulin-like growth factor-I stimulates amino acid transport in a glutamine-deprived human neuroblastoma cell line.
It is still unknown how insulin-like growth factor-I (IGF-I) regulates cancer cell growth in the condition of the limited availability of key nutrients, such as glutamine. We investigated the effects of IGF-I on cell growth and amino acid transport in a glutamine-deprived human neuroblastoma cell line, SK-N-SH. Cell growth was measured, and 3H-labeled amino acid transport was assayed after treatment with or without IGF-I (50 ng/ml) in 2 mM (control) and 100 microM glutamine concentrations. Cell growth rates were dependent on glutamine concentrations. IGF-I stimulated cell growth in both 2 mM and 100 microM glutamine. IGF-I stimulated glutamine transport in 100 microM glutamine with the mechanism of increasing carrier Vmax, but had no effect in 2 mM glutamine. IGF-I also stimulated leucine, glutamate and 2-(methylamino)isobutyric acid transport in 100 microM glutamine. There were significant increases in [3H]thymidine and [3H]leucine incorporation in IGF-I-treated cells in both 2 mM and 100 microM glutamine. These data suggest that IGF-I stimulates cell growth by increasing amino acid transport in the condition of low glutamine levels in a human neuroblastoma cell line. This mechanism may allow to maintain cell growth even in nutrient-deprived tumor tissues.
Wasa
M
M
Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan. wasa@pedsurg.med.osaka-u.ac.jp
Wang
H S
HS
Tazuke
Y
Y
Okada
A
A
D000596:Amino Acids / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000378:metabolism
D000596:Amino Acids; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011500:Protein Synthesis Inhibitors; D005973:Glutamine; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I; D003513:Cycloheximide; D007930:Leucine