ABSTRACT
Certain combinations of oncogenes also cooperate both to immortalize and to transform primary cells, although it is not clear that immortalization is a direct effect of the activities of the genes. Thus, new patterns of gene expression following chromosomal rearrangements or ill-defined epigenetic changes, possibly involving known oncogenes or as yet unidentified loci, are thought to confer important new growth properties upon cells within the mortal population. The influence of culture conditions on the phenotype of the cells after selection for growth in vitro indicates that adaptive responses and differential gene expression likely play significant roles in establishment. The increase in the cytoplasmic abundance of mRNA species encoding Mitogen-Regulated Protein (MRP) and murine leukemia virus proteins has been followed during the senescence and immortalization of mouse embryo cells passed according to a 3T3 regimen. Alternatively, MRP/proliferin could participate more indirectly by influencing the sensitivity of the immortal fibroblasts to another serum growth factor such as insulin-like growth factor.
