Impaired Interleukin-3 mRNA Decay in Autocrine Mast Cell Tumors after Transient Calcium Ionophore Stimulation

Abstract

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.