Transgenic mouse mammary tumors are quite remarkable and quite unique. They are different from the tumors described by Dunn. Animals which express the transgenes commonly found in MuMTV-infected mice develop the Dunn type tumors. So, mice with the int-1 transgene have the alveolar type A tumors that are found in MuMTV infected mice. Animals with the int-2 transgene form hyperplasias which resemble in detail the hormone dependent plaques found in GR/A and DD. They also have type B and papillary tumors.
All other transgenic and knock animals have tumors that do not resemble those described by Dunn. In fact, all other genetically manipulated animals have relatively unique tumor phenotypes. This suggested to us that the genotype determined the mammary tumor phenotype. In a study of over 700 tumors, the myc transgene was found to result in adenocarcinomas with characteristic large dark-staining cells. The ras transgene was associated with papillary transitional carcinomas with small cells. The neu transgene was associated with nodular tumors with intermediate cells.
Additional tumor phenotypes have now been found. TGFa tumors tend to be tubular adenocarcinomas with an inflammatory stroma. Polyoma virus middle T antigen tumors tend to be papillary and are associated with extensive fibrosis. Other examples of transgene-specific tumor phenotypes may be given and are summarized elsewhere and in the table.
The tumor phenotypes found in myc, ras and neu are the most characteristic. They have not been found in mice with other transgenes. Myc is the most dominant transgene. Any combination of myc with another transgene results in tumors with large blue cells
We have the most extensive experience with neu related animals. The solid nodular intermediate cell phenotype is in animals from different founder strains. This is of particular interest since the neu transgene is the murine homologue to c-erb-B2 or Her-2 associated with the comedocarcinomas in humans.
However, most of the transgenic tumors do not have as distinctive characteristics as the myc, ras, and neu tumors. Many different transgenes result adenocarcinomas that are difficult to distinguish from each other. On the other hand, the pattern of tumor is very consistent within the transgenic strain. For example, almost all of the tpr/met tumors are adenocarcinomas , int-2 and PyV-MT tumors are typically papillary and src tumors are typically scirrhous carcinomas.
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