Interleukin-3 mRNA stabilization by a trans-acting mechanism in autocrine tumors lacking interleukin-3 gene rearrangements.
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.
Hirsch
H H
HH
Institute for Medical Microbiology, University of Basel, Switzerland.
Nair
A P
AP
Backenstoss
V
V
Moroni
C
C
D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers; D004261:DNA Replication / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D015321:Gene Rearrangement; D011905:Genes, ras; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008407:Mast Cells; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D017931:DNA Primers; D007377:Interleukin-3; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003609:Dactinomycin; D013936:Thymidine