Responsiveness to insulin is a dominant characteristic in somatic cell hybrids

The mouse melanoma cell line PG19 has been found to be unresponsive to the growth-stimulatory action of insulin, although it responds well to other growth factors present in serum. Insulin stimulates DNA synthesis in mouse embryo fibroblasts, and responsiveness to insulin has been found to be a dominant characteristic in mouse fibroblast x PG19 hybrids. To examine the possibility that the unresponsiveness to insulin of the melanoma cells is attributable to a lack of insulin receptors, we have measured the binding of 125I-labeled insulin to the fibroblasts, melanoma cells, and fibroblast x melanoma hybrids. Insulin binds to the surface of the melanoma cells; however, the binding affinity appears to be lower than that observed for binding to diploid fibroblasts. In addition, the dissociation of insulin from the melanoma cells is not accelerated by excess unbound insulin, a kinetic effect observed in the dissociation of insulin from the fibroblasts and fibroblast x melanoma hybrids. This suggests that the class of insulin receptors characterized by this effect is absent on the PG19 cells, and present on the fibroblasts and fibroblast x PG19 hybrids.