Insertion mutation of the int-1 and int-2 loci by mouse mammary tumor virus in premalignant and malignant neoplasms from the GR mouse strain.
Mouse mammary tumor virus (MMTV)-induced mammary adenocarcinomas can develop from several different premalignant precursors common in GR mice. Insertion mutagenesis of the mammary protooncogenes int-1 and int-2 was studied in this multistep system by analyzing samples from various stages of neoplastic development for novel int-1 and int-2 restriction fragments generated by MMTV provirus integration. int-1 and int-2 insertion mutations were observed in both premalignant lesions and malignant tumors. Some of the tumors with insertion mutations were experimentally derived from insertion mutation-free premalignant precursors. Each class of neoplasm examined had a characteristic frequency of int-1 and int-2 insertion mutations; however, no correspondence was observed between neoplasm morphology and mutation of either gene. These results indicate that insertion mutation of the int-1 and int-2 loci by MMTV provirus can be involved in the earliest identifiable stages of neoplastic development as well as during progression of premalignant lesions to tumors. Insertion mutation of int-1 and int-2 is therefore not stage specific in this system.
Morris
D W
DW
Department of Pathology, School of Medicine, University of California, Davis 95616.
Barry
P A
PA
Bradshaw
H D
HD
Cardiff
R D
RD
D000818:Animals; D015139:Blotting, Southern; D003001:Cloning, Molecular; D004251:DNA Transposable Elements; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009368:Neoplasm Transplantation; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D011519:Proto-Oncogenes; D015183:Restriction Mapping
D004251:DNA Transposable Elements