RETROVIRAL INFECTION ACCELERATES T-LYMPHOMAGENESIS IN E-MU-N-RAS TRANSGENIC MICE BY ACTIVATING C-MYC OR N-MYC
- Author(s)
- Haupt, Y; Harris, AW; Adams, JM;
- Details
- Publication Year 1992-05,Volume 7,Issue #5,Page 981-986
- Journal Title
- ONCOGENE
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- STOCKTON PRESS
- Keywords
- MURINE LEUKEMIA-VIRUS; CELL LYMPHOMAS; PROVIRAL INSERTION; ONCOGENES; GENE; CARCINOGENESIS; INVOLVEMENT; INTEGRATION; MUTATIONS; FREQUENCY
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Creation Date: 1992-05-01 12:00:00