Augmented MYCN Expression Advances the Malignant Phenotype of Human Neuroblastoma Cells: Evidence for Induction of Autocrine Growth Factor Activity1

Amplification and enhanced expression of the MYCN oncogene are thought to contribute to the development and progression of human neuroblastomas. Here, we have transfected human neuroblastoma cells that harbor a single MYCN gene copy with the human MYCN gene driven by a viral enhancer/promoter, and we have compared the properties of the parental and the transfected cells. The transfected cells show an enhanced expression of the exogenous MYCN gene. Unlike the parental cells, they have acquired an increased proliferative potential, induce tumors in nude mice, grow in soft agar, and require low amounts of exogenous growth factors in order to proliferate. The A/yC/V-transfected, but not the parental, cells can synthesize and utilize autocrine growth factor activity. These results demonstrate that enhanced MYCN expres sion contributes to malignant progression of human neuroblastoma cells, conceivably by stimulating the expression of autocrine growth factor activity.