AN INVITRO FIBROBLAST MODEL SYSTEM TO STUDY MYC-DRIVEN TUMOR PROGRESSION

We have utilized fibroblast cell lines to investigate myc-mediated cell transformation and tumour progression. Deregulated myc alleles were introduced into the rat fibroblast cell line, Rat- 1, and a partially-transformed derivative of this cell line termed Rat- 1 (PT). A human c-myc gene coupled to the Moloney murine leukemia virus long terminal repeat was introduced into both cell lines by transfection. The avian MC29 v-myc gene was introduced into the Rat- 1 cell line by retroviral infection using a Moloney murine leukemia recombinant retrovirus. For both cell lines, the introduction of exogenous myc genes resulted in an increased degree of transformation. For the non-tumorigenic Rat- 1 cell line, this also resulted in the acquisition of tumorigenicity, while for the Rat- 1(PT) cell line the degree of tumorigenicity was increased. Various clones were isolated and, for both human c-myc and avian v-myc, the level of myc expression correlated with the degree of transformation and the tumorigenic potential of the cell lines. In addition, both these parameters could be increased by passaging through syngeneic recipients. Our data show that tumour progression may be driven by the deregulated expression of myc genes; that transformation and tumorigenicity correlate with the level of exogenous myc expression; that additional events involving both in vitro and in vivo selection are involved in this process; and that myc expression may increase the cells' metastatic capacity.