Tumors obtained from v-Ha-ras-transformed PB-3c cells are characterized by autocrine interleukin-3 (IL3) expression, which occurs either without (class I tumors) or with enhanced transcription (class II tumors). To address possible post-transcriptional mechanisms of IL3 expression, IL3 mRNA stability was examined in both tumor classes. Increased stability of IL3 mRNA was detected in class I tumor lines (t1/2 > 3 h), whereas rapid decay of IL3 transcripts (t1/2 < 0.5 h) was found in class II tumor lines. In both tumor classes, the c-myc and interleukin-6 transcripts were short-lived. Transcripts of a constitutively expressed IL3 reporter gene were stable in class I tumor cells but unstable in class II tumor cells, suggesting that IL3 mRNA stabilization involved a trans-acting mechanism. Rapid decay of IL3 reporter transcripts was observed in untransformed PB-3c as well as in v-Ha-ras expressing precursor cells linking transcript stabilization to the tumor stage. Reporter transcript stabilization in class I tumor cells correlated with increased IL3 production. Deletion of the AU-rich element from the IL3 reporter gene further augmented IL3 mRNA levels as well as IL3 production, suggesting that the stabilizing mechanism in class I tumor cells is not equivalent to AU-rich element deletion.
Autocrine interleukin-3 (IL-3) expression of v-H-ras transformed mast cell tumors involves either IL-3 mRNA stabilization (class-I tumors) or enhanced IL-3 transcription (class-II tumors). Since calcium ionophores induce IL-3 expression in untransformed PB-3c cells by transcript stabilization, we asked whether class-I tumor could still respond to calcium ionophores. We found that ionomycin treatment further increased IL-3 mRNA expression of class-I tumor cells. Following ionomycin wash-out, IL-3 mRNA decay was slower in class-I tumor cells than in class-II tumor or precursor cell lines (t1/2 > 50 min versus < 20 min, respectively). Somatic cell fusion of the class-I tumor cells with the non-tumorigenic PB-3c cells resulted in reversion to rapid decay after ionomycin wash-out. The data indicate that a recessive defect of IL-3 mRNA degradation can be revealed in class-I tumor cells by transient calcium ionophore stimulation. However, IL-3 mRNA stabilization operating constitutively in class-I tumor cells appears to be distinct from the ionomycin induced process.
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