Diminished epidermal growth factor binding by neurofibromatosis fibroblasts

Neurofibromatosis (NF) is an autosomal dominant disease characterized by growth abnormalities of epithelial, mesothelial, and endothelial elements. We recently reported abnormal growth and morphology of NF fibroblasts in tissue culture. Because epidermal growth factor (EGF) is known to stimulate the growth of fibroblasts in tissue culture, we studied the binding of commercial iodine 125-labeled EGF to age- and passage-matched confluent NF (N = 6) and normal (N = 4) fibroblasts. Fibroblasts were maintained at 37 degrees C for 2, 30, 60, 120, and 240 minutes in a medium in which the cells grow slowly (Dulbecco's Eagle medium) and one in which they grow normally (Ham's F-12 medium). Binding assays were done in both serum-free media according to accepted procedures. The EGF binding did not differ in the two media, and pooled data are presented. These data demonstrate no significant differences in the early binding of EGF to normal and NF fibroblasts (4,682 +/- 1,092 versus 3,441 +/- 826 cpm/10(6) cells; 20,000 cpm/ng; p > 0.15 at 30 minutes). At one hour, however, differences suggestive of abnormal EGF binding become apparent (12,495 +/- 1,989 versus 3,172 +/- 853 cpm/10(6) cells; 20,000 cpm/ng; p < 0.0025). We conclude that there may be a membrane defect in NF which is reflected by diminished EGF binding.