Impaired interleukin-3 mRNA decay in autocrine mast cell tumors after transient calcium ionophore stimulation.
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.
Hirsch
H H
HH
Institute for Medical Microbiology of the University of Basel, Switzerland.
Backenstoss
V
V
Moroni
C
C
D000818:Animals; D015152:Blotting, Northern; D015220:Calcium Channels / Q000378:metabolism*; D002459:Cell Fusion; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D007377:Interleukin-3 / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology*; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D011061:Poly A / Q000378:metabolism; D011071:Poly T / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D007377:Interleukin-3; D007476:Ionophores; D012333:RNA, Messenger; D003609:Dactinomycin; D011061:Poly A; D011071:Poly T; D015759:Ionomycin; D003513:Cycloheximide