Analysis of Multistep Mammary Tumorigenesis in WNT-1 Transgenic Mice.
Abstract
Mouse mammary tumor virus is used as a mutagen in transgenic mice that carry an activated Wnt-1 gene, to produce additional events such as activation of a second oncogene by nearby insertion of proviral DNA. In about 55% of the mammary tumors having new proviral insertions, no known targets of MMTV mutations or known Fgf genes are affected, implicating the involvement of other proto-oncogenes. In order to identify one of the activated proto-oncogenes from this group of tumors, the cellular sequences flanking a new proviral insertion site from tumor 76 was cloned, the insert mapped, and repeat free fragments isolated. Southern blots of tumor DNAs probed with the cellular fragments show rearrangements due to MMTV proviral insertions within this locus in 12 of 85 tumors analyzed. These results indicate that this is a common insertion site for MMTV. Since northern analysis and exon trapping failed to identify an activated gene within the cloned region, the region downstream is being cloned and characterized. No known targets of MMTV mutations or members of the FGF family seem to be activated in these tumors. Therefore it is likely that we would find a novel or unexpected proto-oncogene activated in these tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1995
- Accession Number
- ADA302270
Entities
People
- Deepa Shankar
Organizations
- Children's Hospital Los Angeles