Induction of (2'-5')oligoadenylate synthetase in serum-starved HeLa S3 cells by growth factors and its role in growth regulation.
When serum-starved HeLa S3 cells were stimulated to proliferate by addition of fetal calf serum (FCS), (2'-5')oligoadenylate synthetase (2-5A synthetase) activity was induced. Although no interferon (IFN) activity was detectable in the HeLa S3 cell-conditioned culture medium after growth stimulation, addition of anti-IFN-beta monoclonal antibody inhibited both the expression of the 2-5A synthetase gene and the production of the enzyme, suggesting that endogenous IFN-beta was involved in 2-5A synthetase induction. Purified preparations of three growth factors, epidermal growth factor, platelet-derived growth factor, and insulin, also induced 2-5A synthetase through IFN-beta. When serum-starved HeLa S3 cells were treated with FCS, DNA synthesis was initiated synchronously, with peaks after 12 and 32 h, although the level of 2-5A synthetase reached a maximum after the first peak of DNA synthesis. Inhibition of 2-5A synthetase induction by anti-IFN-beta antibody enhanced the second, but not the first cycle of DNA synthesis. These results suggested that in HeLa S3 cells, after stimulation with growth factors the IFN/2-5A synthetase system played a role in cell growth negative regulatory mechanisms.
Iwata
A
A
Department of Molecular and Cellular Virology, Kyoto University.
Kohno
M
M
Sokawa
Y
Y
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000235:genetics; D000911:Antibodies, Monoclonal; D004247:DNA / Q000096:biosynthesis; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007370:Interferon Type I / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D006133:Growth Substances; D007370:Interferon Type I; D004247:DNA; D015088:2',5'-Oligoadenylate Synthetase