Suppressible and nonsuppressible autocrine mast cell tumors are distinguished by insertion of an endogenous retroviral element (IAP) into the interleukin 3 gene.
After v-H-ras expression, the interleukin 3 (IL-3)-dependent PB-3c mast cells progress in vivo to two different classes of IL-3 autocrine tumors. Class I tumors show a germline configuration of the IL-3 gene and represent more than 90% of tumors analyzed so far. Somatic cell fusion of class I tumor lines with the nontumorigenic parental PB-3c resulted in loss of oncogenic IL-3 expression by a posttranscriptional mechanism with concomitant tumor suppression. Class II tumors arise rarely and contain an insertion in one IL-3 allele. This alteration was linked to enhanced IL-3 gene transcription. For one tumor, the insertion was shown to be an endogenous retroviral element (intracisternal A-particle). Cell hybrids of class II tumors with PB-3c remained IL-3 independent, expressed IL-3, and formed tumors rapidly. These results suggest that the v-H-ras oncogene synergizes with a recessive and a dominant lesion in class I and II tumors, respectively, both of which lead to the autocrine production of IL-3.
Hirsch
H H
HH
Institut für Medizinische Mikrobiologie, Universität Basel, Switzerland.
Nair
A P
AP
Moroni
C
C
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004277:DNA, Single-Stranded; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D007426:Genes, Intracisternal A-Particle; D011905:Genes, ras; D006822:Hybrid Cells; D007377:Interleukin-3 / Q000235:genetics* / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004277:DNA, Single-Stranded; D007377:Interleukin-3