The long term interest of my laboratory is understanding carcinogenesis at the molecular level. Presently we are focusing on the induction of lymphomas in rats. We have shown that 6 of 32 such lymphomas have MLV proviruses integrated adjacent to c-myc, and have isolated a bacteriophage Lambda clone of one lymphoma myc gene and its flanking provirus, During the next review period this clone will be tested in a primary cell/two gene transfection assay to determine if proviral insertion has activated the oncogenic potential of c-myc, and in vitro recombinants between normal and lymphoma myc genes will be constructed and tested in this assay to localize the cause of this oncogenic activity. RNA gel blot hybridization and analysis of fusions between myc promotors and the E. coli chloramphenicol acetyltransferase gene will be used to analyze alterations in the regulation of myc transcription. Southern blot analysis, DNA sequence analysis and heteroduplex analysis will be used to localize the site and determine the orientation of proviruses integrated adjacent to c-myc and to look for alterations in the myc sequences other than proviral insertion. The NIH 3T3 cell transfection assay will be used to search for activated oncogenes in MLV-induced lymphoma DNAs.
| Shin, S; Steffen, D L (1993) Frequent activation of the lck gene by promoter insertion and aberrant splicing in murine leukemia virus-induced rat lymphomas. Oncogene 8:141-9 |
| Hildebrandt, J D; Lederman, L; Steffen, D L (1991) Effect of ras-gene transformation on the inhibition of NIH3T3 cell growth by pertussis toxin. Mol Endocrinol 5:1101-8 |
| Steffen, D L; Nacar, E Q (1988) Nucleotide sequence of the first exon of the rat c-myc gene: proviral insertions in murine leukemia virus-induced lymphomas do not affect exon 1. Virology 164:55-63 |
| Vijaya, S; Steffen, D L; Kozak, C et al. (1987) Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas. J Virol 61:1164-70 |
| Vijaya, S; Steffen, D L; Robinson, H L (1986) Acceptor sites for retroviral integrations map near DNase I-hypersensitive sites in chromatin. J Virol 60:683-92 |
