Sustained expression of the human protooncogene MYCN rescues rat embryo cells from senescence

Amplification of the human gene MYCN may play a role in the malignant progression of human neuroblastomas. In pursuit of this possibility, previous studies have shown that the abundant expression of MYCN in cultured cells can elicit several aspects of the transformed phenotype. We now extend those findings by demonstrating that rat embryo cells transfected with MYCN can proliferate for at least 200 generations. Isolation of established cells was dependent on high expression of MYCN and on biological selection to eliminate untransfected cells. The established cells were not tumorigenic in syngeneic rats or athymic mice, failed to grow in soft agar, and required relatively high concentrations of serum for proliferation in culture. Our results show that enhanced expression of MYCN can rescue normal cells from senescence, add to the credentials of MYCN as an authentic protooncogene, and identify an additional biological activity that can be used in the characterization of MYCN.