Rodent fibroblast tumours expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression

Abstract

The effects of expression of human c-myc and both mutated (T24) and normal forms of human Ha-ras-1 were studied in an aneuploid rat fibroblast line (208F). Mutated T24 Ha-ras was also studied in a near-diploid cell derived from early passage Chinese hamster lung fibroblasts (CHL). In contrast to the parental fibroblasts, cells expressing any of the human oncogenes engendered rapidly growing tumours in immune-suppressed animals. Blood- and lymph-borne metastases were observed from both ras- and myc-expressing cells. In general ras-expressing cells were more aggressive than those expressing myc. In the 208F background, expression of c-myc was associated with an incidence of mitosis similar to that in tumours expressing T24 Ha-ras, but incidence of single cell death by apoptosis was higher. Quantitatively, expression of human oncogene mRNA was constant during growth in vivo, and similar to that sometimes observed in human neoplasms. Of 9 endogenous proto-oncogenes, 7 showed no change in expression from the parental fibroblasts, but c-abl and c-fos were strongly expressed in all cells expressing human ras or myc. Thus these tumorigenic cells, although transfected with single human oncogenes, all expressed oncogenes with both nuclear- and membrane-associated products.