Normal human mesothelial cells and fibroblasts transfected with the EJras oncogene become EGF-independent, but are not malignantly transformed.

The nature of the lesion in growth control exerted by the cancer-derived c-H-ras mutation, EJ-ras, and its transforming potential in diploid cells are both poorly understood. We introduced EJ-ras into normal, diploid human mesothelial cells and fibroblasts and obtained transfectants expressing p21EJ-ras. All clones examined were independent of EGF for rapid growth, and all secreted an EGF-like mitogen into the medium at levels sufficient to satisfy the EGF requirement of normal cells. The EJ-ras transfectants were not altered with respect to any other growth requirement, and they were not transformed. Eleven clones tested all retained a finite replicative lifespan which, in most cases, was the same as that of the parent cell strain. Three transfectants tested were not tumorigenic in nude mice. Thus p21EJ-ras can circumvent an important mitogenic signal pathway in human cells. Nevertheless, neither the secretion of an autocrine growth factor nor any other effect of p21EJ-ras serves to malignantly transform normal human cells, in contrast to the susceptibility of some established rodent cell lines to transformation by these mechanisms.