Tumor suppression involves down-regulation of interleukin 3 expression in hybrids between autocrine mastocytoma and interleukin 3-dependent parental mast cells.
Interleukin 3 (IL-3)-dependent PB-3c mouse mastocytes can be transformed by the v-Ha-ras oncogene to generate autocrine IL-3-producing mastocytomas. Hybrid cell lines were constructed by fusing an IL-3-producing mastocytoma cell line with its IL-3-dependent normal parental cell. Unlike the mastocytoma parent cell line, hybrid cell lines required growth factor for in vitro proliferation, indicating that the IL-3-dependent phenotype is dominant. IL-3 mRNA, expressed at high levels in the tumor cells, appeared down-regulated in the cell hybrids. In contrast, p21v-Ha-ras levels were not reduced in the hybrids. The hybrid lines generated tumors in vivo with drastically prolonged latency times when compared to the tumor parent (10 versus 2 weeks). We propose that down-regulation of IL-3 mRNA production after cell fusion is responsible for the loss of growth autonomy in the hybrids and is likely to play a role in the partial suppression of tumor formation in vivo. Our data are consistent with the hypothesis that a tumor suppressor, present in PB-3c cells, acts as a negative regulator of IL-3 expression.
Diamantis
I D
ID
Institut für Medizinische Mikrobiologie, Basel, Switzerland.
Nair
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AP
Hirsch
H H
HH
Moroni
C
C
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D007377:Interleukin-3 / Q000235:genetics* / Q000502:physiology; D008407:Mast Cells / Q000166:cytology*; D012515:Mast-Cell Sarcoma / Q000235:genetics*; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D007377:Interleukin-3; D012333:RNA, Messenger