Regulation of proliferation in a murine colony-stimulating factor-dependent myeloid cell line: Superinduction of C-fos by the growth inhibitor 8-Br-cyclic adenosine 3?:5? monophosphate
- 1 November 1988
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 38 (3) , 145-153
- https://doi.org/10.1002/jcb.240380302
Abstract
We have investigated the effect of 8‐Br‐cyclic adenosine 3′:5′ monophosphate (cAMP), a pharmacological activator of cAMP‐dependent protein kinase, on the proliferation and the nuclear proto‐oncogene induction in a murine granulocyte macrophage colony‐stimulating factor (GM‐CSF)‐dependent myeloid cell line. Cells were growth arrested by granulocyte macrophage colony‐stimulating factor and serum deprivation and were allowed to proceed in the cell cycle by addition of the lymphokine in the presence or absence of 8‐Br‐cAMP.3H‐thymidine incorporation assays showed that addition of 8‐Br‐cAMP inhibited the entry of cells into S phase and the subsequent proliferation. Northern analysis showed that 8‐Br‐cAMP had opposite effects on c‐fos and c‐myc mRNA induction. 8‐Br‐cAMP induced c‐fos in the absence of any GM‐CSF. In the presence of GM‐CSF, c‐fos mRNA was superinduced (30‐fold induction compared to four‐ to fivefold by each signal alone). On the contrary, 8‐Br‐cAMP was not able to induce c‐myc in the absence of growth factor and hardly interfered with the induction of c‐myc by GM‐CSF. Phorbol myristate acetate (PMA), a pharmacological activator of the lipid and CA++ ‐dependent protein kinase C, was shown to induce nuclear proto‐oncogene mRNA in the GM‐CSF‐dependent cell line. We investigated the effect of 8‐Br‐cAMP on PMA‐induced c‐fos and c‐myc mRNA levels. When both cAMP dependent and lipid‐dependent kinase systems were co‐stimulated in the absence of GM‐CSF, c‐fos message was again superinduced (60‐fold induction). On the contrary, c‐myc message induction by PMA was inhibited by 80% by coactivation of cAMP‐dependent protein kinase with 8‐Br‐cAMP. Our data indicate that an antiproliferative signal induces or even superinduces c‐fos message and hardly interferes with c‐myc induction, suggesting that the intracellular pathways resulting in c‐fos and c‐myc induction may be distinct and that two different pathways can lead to c‐fos induction, with synergistic effects when both are activated.Keywords
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