Retroviral infection accelerates T lymphomagenesis in E mu-N-ras transgenic mice by activating c-myc or N-myc.
Transgenic mice bearing a mutant, activated N-ras oncogene directed to express within hematopoietic cells by an immunoglobulin enhancer (E mu) sporadically develop T-cell lymphomas and non-lymphoid tumors that may be of macrophage origin. To identify genes that can collaborate with N-ras in hematopoietic neoplasia, Moloney murine leukemia virus was used as an insertional mutagen. Infection of newborn E mu-N-ras mice with the virus greatly accelerated tumorigenesis, and nearly all the tumors proved to be T-cell lymphomas. Their variable surface phenotype (CD4+CD8-, CD4+CD8+ and CD4-CD8-) suggested that cells at several stages of T-cell development were susceptible to tumorigenesis. Southern blot analysis revealed that 68% of the tumors bore a proviral insert 5' to the c-myc gene, while 13% had an insert within the 3' untranslated region of the N-myc gene. Insertion was associated with elevated expression of these genes. Hence, activation of a myc gene appears to be the dominant pathway to tumorigenesis by insertional mutagenesis in lymphoid cells expressing a mutant ras gene. However, since many of the tumors were not transplantable, even the partnership of myc and ras may not suffice for full lymphoid malignancy.
Haupt
Y
Y
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Harris
A W
AW
Adams
J M
JM
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002874:Chromosome Mapping; D015967:Gene Expression Regulation, Viral; D015321:Gene Rearrangement; D016259:Genes, myc / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology*; D016399:Lymphoma, T-Cell / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus; D016254:Mutagenesis, Insertional; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D011533:Proviruses / Q000502:physiology
D016271:Proto-Oncogene Proteins c-myc