Cooperation between Multiple Oncogenes in Rodent Embryo Fibroblasts: an Experimental Model of Tumor Progression?

Abstract

Publisher Summary Stepwise progression of tumoral diseases toward increased invasiveness, hormonal independence, and resistance to chemical and physical treatment is an all-too-common phenomenon that has been analyzed in various experimental systems. The stepwise character and apparent irreversibility of these phenotypic changes would be most easily accounted by a sequential accumulation of genetic alterations. Alterations of cellular genes associated with malignancy (oncogenes) are recently identified, first as a result of the natural capacity of retroviruses for gene transduction and subsequently by the transfection of genomic DNA from human tumors into mouse cells. Unlike most retroviruses, oncogenic DNA viruses that have been analyzed so far appear to require more than one gene to establish and maintain neoplastic transformation. This was extensively documented for polyoma viruses and adenoviruses, and more recent observations suggest a similar situation for two herpesviruses— herpes simplex type 2 and Epstein–Barr virus. Experimental evidence summarized in this chapter defines an early stage of the oncogenic transformation process induced by the plt and E1A oncogenes and, at least under some defined conditions of expression, by the rearranged forms of the myc gene.