Malignant transformation of rat cells by the polyomavirus middle T gene

To gain an insight into the molecular mechanism of cooperation between the polyomavirus middle T gene and cellular genes in the tumorigenic process, we have examined various properties of rat cell lines transformed by middle T alone. Middle T transformants display a phenotype ranging from nontumorigenic (flat) to fully transformed (tumorigenic) and the phenotype of a given cell line correlates very well with its cellular level of middle T antigen. Highly transformed, tumorigenic variants arise spontaneously in the flat cells during their growth with a mutation rate of 2.2 X 10(-5) per cell per generation. These variants contain elevated levels of both middle T antigen and middle T transcripts, suggesting that fully transformed cells arise as a consequence of an efficient mode of viral gene expression.