Mast cells sensitive to v-H-ras transformation are hyperinducible for interleukin 3 expression and have lost tumor-suppressor activity.
Subcloning of interleukin 3 (IL-3)-dependent PB-3c mastocyte cells revealed two populations, of which only one is sensitive to oncogenic transformation by v-H-ras. The corresponding tumors produce IL-3 and grow in vitro in the absence of exogenous IL-3 [Nair, A.P.K., Diamantis, I.D., Conscience, J.F., Kindler, V., Hofer, P. & Moroni, Ch. (1989). Mol. Cell. Biol., 9, 1183-1190]. In the present investigation, IL-3 gene regulation was compared in ras transformable (rT) and ras nontransformable (rNT) lines. We report that upon expression of v-H-ras rT clones but not rNT clones express low levels of IL-3 mRNA as detected by reverse polymerase chain reaction. Treatment with ionomycin, a calcium ionophore, induced high levels of IL-3 expression only in ras-expressing rT clones. Somatic cell fusion between the rNT clone 20 and the IL-3-expressing mastocytoma line V2D1 led to down-regulation of IL-3 expression and to the requirement for exogenous IL-3 for in vitro growth and tumor suppression. In contrast, rT clone 15 lacked tumor-suppressor activity and failed to down-regulate IL-3 expression in somatic hybrids which grew in vitro without added IL-3. Our results indicate that IL-3 gene expression is a critical determinant for the generation of v-H-ras-induced mast cell tumors and show that disturbances in IL-3 gene regulation can be detected already at the premalignant level in v-H-ras transformation-sensitive cells.
Nair
A P
AP
Institute for Medical Microbiology, University of Basle, Switzerland.
Hirsch
H H
HH
Moroni
C
C
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000032:analysis; D011905:Genes, ras; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*; D012515:Mast-Cell Sarcoma / Q000517:prevention & control*; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis
D007377:Interleukin-3; D012333:RNA, Messenger; D015759:Ionomycin; D004247:DNA