Transgenic Mice and Oncogenesis

The creation of transgenic mice carrying specific cancer-promoting genes has opened an exciting new era in oncology. The biological effects of an individual oncogene on diverse cell types can now be assessed directly within the living animal. While transgenic animals bear the introduced oncogene in every tissue, expression of that gene may either be widespread or directed to a particular cell lineage, depending upon the regulatory sequences chosen. The transgene should behave identically in every animal of an established lineage and, indeed, perhaps in every cell of a given type. Thus, a well-characterized transgenic line becomes a permanent resource. Perhaps the most significant opportunity provided by these transgenic animals is the possibility of exploring the pre-neoplastic state. One can attempt to assess whether an oncogene has perturbed differentiation within particular lineages. The perturbations may help to delineate early matu­ ration stages and to clarify how differentiation is controlled. Thus, new insights may emerge regarding the normal biological functions of proto­ oncogenes. The rules for oncogene cooperativity can also be evaluated within diverse cell types. For example, one can isolate the relevant cells from a pre-neoplastic animal bearing an oncogene and attempt to trans­ form them fully in vitro with retroviruses carrying other oncogenes. Alter­ natively, the second oncogene could be introduced simply by breeding mice of two independent transgenic lines. While the study of transgenic oncogenes is still in its infancy, major new insights have already been gained. This chapter briefly summarizes how transgenic animals are produced, and then considers our current state of