Calcium-dependent and oncogenic IL-3 mRNA stabilization can be distinguished pharmacologically and by sequence...

In interleukin-3 (IL-3)-dependent PB-3c mast cells, the normally short-lived IL-3 mRNA is stabilized upon calcium-ionophore treatment or following v-H-ras induced oncogenesis. We compared the underlying stabilization mechanisms by analysing the response to the post-transcriptionally acting drugs cyclosporin A (CsA), FK506 and SB202190. Stable IL-3 transcripts in the PB-3c-derived tumour cell line V2D1 decayed in response to CsA and FK506, but not in response to SB202190. Transcripts stabilized by elevating intracellular calcium levels in PB-3c cells were destabilized in response to all three drugs. In PB-3c cells, six AUUUA pentamers within the AU-rich element were sufficient to confer responsiveness to calcium-ionophore and CsA treatment. In V2D1 tumour cells, sensitivity to CsA required additional nucleotides flanking these pentamers. Our data suggest that IL-3 mRNA stabilization by either calcium-dependent or oncogenic pathways involves different intracellular mechanisms.