A v-H-ras-dependent hemopoietic tumor model involving progression from a clonal stage of transformation competence to autocrine interleukin 3 production.
Autocrine interleukin 3 (IL-3)-secreting tumors were generated from an IL-3-dependent mouse mast cell line (PB-3c) after introduction of the v-H-ras oncogene. Tumor progression was characterized by four distinct phenotypes. The first corresponded to immortalized mast cells unresponsive to the oncogenic effect of v-H-ras. The second was expressed in a clonable subpopulation of PB-3c cells and was marked by the competence to form v-H-ras-dependent tumors (immortalized transformation competence). The third was a direct effect of v-H-ras expression on all PB-3c cells and was characterized in vitro by a reduced IL-3 requirement. Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation. Northern (RNA) blot analysis and an RNase A-T1 protection assay showed that IL-3 production was strictly associated with the tumor phenotype. Two of six tumors showed an alteration at the 5' region of the IL-3 gene. We conclude that v-H-ras required complementation by IL-3 gene rearrangement or an alternate event to generate autocrine mastocytomas.
Nair
A P
AP
Friedrich Miescher-Institut, Basel, Switzerland.
Diamantis
I D
ID
Conscience
J F
JF
Kindler
V
V
Hofer
P
P
Moroni
C
C
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D011905:Genes, ras; D005816:Genetic Complementation Test; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000235:genetics; D012515:Mast-Cell Sarcoma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D010641:Phenotype
D007377:Interleukin-3