| Abstract: |
Interferons are regulatory secretory proteins that have a variety of biological activities, including antiproliferative actions against tumor cell lines and tumors in vivo. Among the several interferon-inducible genes, modulation of 2′-5′-oligoadenylate synthetase expression has been the focus of considerable attention because of its implication in growth regulation. In the studies presented here, we report growth inhibition of A431 cells by γ-interferon and provide new evidence to support the possible involvement of 2′-5′-oligoadenylate synthetase. We observed that the antiproliferative effect of γ-interferon on cultures of A431 cells was accompanied by prolongation of G0-Gi phase and profound morphological changes, which were progressively prominent from day 4 onward. The levels of 2′-5′-oligoadenylate synthetase enzyme activity and mRNA were significantly elevated following γ-interferon treatment and correlated well with the kinetics of growth-inhibitory effects. There were differential induction and expression of different isoenzyme forms of 2′-5′-oligoadenylate synthetase: the Mt 100,000 and Mr 40,000 proteins were induced maximally to varying degree by day 4, with subsequent decline; in contrast, the Mr 67,000 protein was induced late and remained high up to day 9 after γ-interferon treatment. In accord with these observations, fractionation of enzymatic activity also revealed differences in the enzyme activities of 2′-5′-oligoadenylate synthetase forms from control and treated cells. Therefore, these observations demonstrate the existence of possible differential regulation of 2′-5′-oligoadenylate synthetase isoenzymes and strengthen the concept that growth inhibition of cells may be mediated via induction of 2′-5′-oligoadenylate synthetase. © 1989, American Association for Cancer Research. All rights reserved. |
| Keywords: |
human cell; cell division; cell line; tumor cells, cultured; time factors; kinetics; gamma interferon; cell culture; interferon-gamma, recombinant; tumor cell; enzyme induction; growth inhibition; isoenzyme; human; priority journal; support, u.s. gov't, p.h.s.; 2',5'-oligoadenylate synthetase; 2',5' oligoadenylate synthetase
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