INTERLEUKIN-3 MESSENGER-RNA STABILIZATION BY A TRANS-ACTING MECHANISMIN AUTOCRINE TUMORS LACKING INTERLEUKIN-3 GENE REARRANGEMENTS

Tumors obtained from v-Ha-ras-transformed PB-3c cells are characterize d by autocrine interleukin-3 (IL3) expression, which occurs either wit hout (class I tumors) or with enhanced transcription (class II tumors) . To address possible post-transcriptional mechanisms of IL3 expressio n, IL3 mRNA stability was examined in both tumor classes. Increased st ability of IL3 mRNA was detected in class I tumor lines (t(1/2) > 3 h) , whereas rapid decay of IL3 transcripts (t(1/2) < 0.5 h) was found in class II tumor lines. In both tumor classes, the c-myc and interleuki n-6 transcripts were short-lived. Transcripts of a constitutively expr essed IL3 reporter gene were stable in class I tumor cells but unstabl e in class II tumor cells, suggesting that IL3 mRNA stabilization invo lved 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 wi th increased IL3 production. Deletion of the AU-rich element from the IL3 reporter gene further augmented IL3 mRNA levels as well as IL3 pro duction, suggesting that the stabilizing mechanism in class I tumor ce lls is not equivalent to AU-rich element deletion.