AUTOCRINE TRANSFORMATION OF HEMATOPOIETIC-CELLS RESULTING FROM CYTOKINE MESSAGE STABILIZATION AFTER INTRACISTERNAL-A PARTICLE TRANSPOSITION

Cell lines that no longer require exogenous interleukin 3 (IL-3) for g rowth were isolated from an IL-3-dependent cell tine that possesses ch aracteristics of early lymphoid cells. Unlike the parental cells (FL5. 12), these autocrine transformed lines (FL-IL3-R) constitutively secre ted IL-3, were rearranged at the IL-3 locus and formed tumors upon inj ection into syngeneic mice. The rearrangement and IL-3 expression resu lted from the transposition of an intracisternal A particle (IAP) prov irus into the 3' untranslated region of the IL-3 gene. This region con tained ATTTA sequence motifs that have been associated with cytokine a nd oncogene mRNA instability. IL-3 transcripts from the autocrine tran sformed cell lines had a longer half-life than similar transcripts iso lated from either phorbol ester-stimulated T cells or the WEHI-3B myel omonocytic cell line. IAP proviral transposition did not alter the tra nscription rate of the IL-3 gene in FL-IL3-R cells. Therefore, IAP pro viral transposition can activate IL-3 gene expression by prolonging mR NA stability, and this mechanism can contribute to the autocrine trans formation of the hemopoietic cells.