An experimental model for oncogene activation during tumor progression in vivo

Tumor progression usually involves a complex pattern of molecular alterations. In many human tumors oncogene amplification or activation has been associated with advanced stages of cancer. Transfection studies have demonstrated the ability of several cellular oncogenes to induce a more malignant phenotype in transformed cells. We have examined the role of c-myc in tumor progression in rat tracheal cell culture, and in rat skin tumors induced by ionizing radiation. In the latter in vivo model, c-myc amplification was found to occur as a function of tumor size. Serial biopsies of growing tumors confirmed the trend toward increased gene copy number with time and stage of progression. This effect was specific for the c-myc gene, in epithelial tumors. Evidence was found for a role of tumor heterogeneity and evolution of tumor cell subpopulations in determining the oncogene activation profile of individual tumors.