Abrogation of factor-dependence in two IL-3-dependent cell lines can occur by two distinct mechanisms.
We have investigated the mechanisms of abrogation of factor-dependence of lymphoid (FL5.12) and myeloid (FDC-P1) interleukin-3 (IL-3)-dependent cell lines following infection of the cells with retroviruses that encode different oncogenes and immediate selection of IL-3-independent growth. As previously reported by others, Abelson-MuLV (Ab-MuLV) transforms both cell lines to factor-independence, and the transformed cells express the viral oncogene, do not produce IL-3, and are tumorigenic. In contrast, IL-3-independent lymphoid and myeloid cell lines recovered after infection with retroviruses that encode v-src or v-fms oncogenes lacked the v-src or v-fms provirus. Three of seven IL-3-independent transformants were rearranged at the IL-3 locus, produced IL-3-specific mRNA, secreted IL-3 into the culture medium, and grew better in the presence of IL-3. These IL-3-independent transformants produced tumors upon inoculation into nude mice, albeit with longer latent periods than Ab-MuLV transformants. The expression of hematopoietic cell markers was compared in parental and IL-3-independent transformants by immunofluorescence and analysis of mRNA levels. Significant elevation of LFA-1 and MHC class I molecules and loss of expression of IL-2-receptor molecules was detected in most IL-3-independent transformants. These differences in antigen expression indicate that additional phenotypic changes accompany transformation to factor-independence.
McCubrey
J
J
Department of Microbiology and Immunology, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
Holland
G
G
McKearn
J
J
Risser
R
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002874:Chromosome Mapping; D015321:Gene Rearrangement; D005814:Genes, Viral; D007377:Interleukin-3 / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes; D011533:Proviruses / Q000235:genetics; D014412:Tumor Virus Infections / Q000473:pathology*
D007377:Interleukin-3