Autocrine transformation of hemopoietic cells resulting from cytokine message stabilization after intracisternal A particle transposition.
Cell lines that no longer require exogenous interleukin 3 (IL-3) for growth were isolated from an IL-3-dependent cell line that possesses characteristics of early lymphoid cells. Unlike the parental cells (FL5.12), these autocrine transformed lines (FL-IL3-R) constitutively secreted IL-3, were rearranged at the IL-3 locus and formed tumors upon injection into syngeneic mice. The rearrangement and IL-3 expression resulted from the transposition of an intracisternal A particle (IAP) provirus into the 3' untranslated region of the IL-3 gene. This region contained ATTTA sequence motifs that have been associated with cytokine and oncogene mRNA instability. IL-3 transcripts from the autocrine transformed cell lines had a longer half-life than similar transcripts isolated from either phorbol ester-stimulated T cells or the WEHI-3B myelomonocytic cell line. IAP proviral transposition did not alter the transcription rate of the IL-3 gene in FL-IL3-R cells. Therefore, IAP proviral transposition can activate IL-3 gene expression by prolonging mRNA stability, and this mechanism can contribute to the autocrine transformation of the hemopoietic cells.
Algate
P A
PA
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858.
McCubrey
J A
JA
D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002874:Chromosome Mapping; D015870:Gene Expression; D015321:Gene Rearrangement; D007426:Genes, Intracisternal A-Particle; D006410:Hematopoiesis; D007377:Interleukin-3 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D007377:Interleukin-3