Discussion

Similarity Difference
Development of cancer consistent with multi-hit kinetics. Some transgenes appear to be associated with one-hit kinetics.

Development of cancer consistent with multi-hit kinetics. Although the development of mammary cancers in mice can be explosive, it is clear that the insertion of a single oncogene into the mouse genome is insufficient for the development of malignancy. All models studied thus far involve a multistep progression that supports the notion that tumorigenesis, even in these special mice, requires multiple hits (Cardiff, 1995). The introduction of two or more transgenes generally accelerates the neoplastic process (Cardiff et al., 1991). Examples of the tumors produced by multiple transgenes in this collection are:

3.1. Growth factors
3.2. Receptors
3.4. Cell Cycle

Comparative pathology of mammary tumorigenesis in transgenic mice.
Cardiff RD, Munn RJ
Cancer Lett 1995 Mar 23;90(1):13-9

Mammary tumors arise in transgenic mice bearing growth factors, proto-oncogenes, oncogenes and tumor suppressor genes. The tumors arise from hyperplasias. The tumor natural history and histogenesis are oncogene specific. Interactions between oncogenes may impede or accelerate tumorigenesis.
Transgenic oncogene mice. Tumor phenotype predicts genotype.
Cardiff RD, Sinn E, Muller W, Leder P
Am J Pathol 1991 Sep;139(3):495-501

The hypothesis that oncogenes influence tumor phenotype was tested by examining slides from 607 mammary tumors from 407 transgenic mice bearing the ras, myc, and/or neu oncogenes. Most tumors (91%) had patterns (phenotypes) that could not be classified by Dunn's standard nomenclature. The nonstandard tumors were described as eosinophilic small cell (SC), basophilic large cell (LC), or pale intermediate cell (IC). The SC tumor was associated with ras, the LC was associated with myc, and the IC was associated with neu, with specificities more than .90 and sensitivities ranging from .99 to .48. Thus, the tumor phenotype could be used to predict which oncogene was present in the animal. The presence of myc in combination with either ras or neu resulted in the predominance of LC tumors and accelerated tumorigenesis. The combination of ras and neu resulted in a decreased tumor incidence. Thus, knowledge of the oncogenes that were present could be used to predict the natural history of the disease.