Tumorigenesis in transgenic mice: Identification and characterization of synergizing oncogenes

AbstractTransgenic mice carrying oncogenes present a useful model with which to assess the tissue‐specific action of oncogenes. These mice are usually predisposed to a specific type of neoplastic growth. The tumors that arise are usually monoclonal in origin and become only apparent after a variable latency period, suggesting that additional events are required for tumor formation. Identification of these additional events is highly relevant: it might give access to the genes that can synergize with a preselected oncogene in tumorigenesis and could facilitate the identification of the biochemical pathways in which these genes act. Retroviruses can be instrumental in identifying cooperating oncogenes. Proto‐oncogene activation or tumor suppressor gene inactivation by insertional mutagenesis is an important mechanism by which the non‐acute transforming retroviruses can induce tumors in several species. Owing to the sequence tag provided by the provirus, the relevant proto‐oncogene can be directly identified by cloning of the DNA flanking the proviral insertion site. We have exploited this potential of retroviruses by infecting Eμ‐pim‐1 and Eμ‐myc transgenic mice, which are predispose