Growth factor regulation of membrane transport in human fibroblasts and its relationship to stimulation of DNA synthesis.

Serum stimulation of serum-deprived or density-inhibited normal cells enhances the level of various nutrient and ionic transport systems. Certain of these systems have been implicated in the regulation of cell proliferation. However, the use of serum stimulation to activate quiescent cells leads to enhancement of numerous transport systems with little understanding of which component or components of serum are related to activation of which transport systems. In this study we attempt to identify the specific effect of three known growth promoting factors (insulin, dexamethasone and epidermal growth factor [EGF]) on the activation of four membrane transport systems (A-amino acids, L-amino acids, glucose and K+) in normal and SV40-transformed WI38 human fibroblasts. We have also evaluated the effect of these growth factors on the stimulation of DNA synthesis in growth factor deprived cells. Thus, we can correlate the effect on a given transport system with the relative mitogenic stimulation produced by the growth factor. We conclude a) that a growth factor can effect a transport system differently in a normal versus transformed cell, b) that a specific growth factor can effect multiple transport systems and, c) with the exception of K+ transport, enhanced transport induced by a given growth factor does not necessarily correlate with the mitogenic potency of the growth factor. This latter point is of particular significance since the activation of K+ transport reflects, based on other studies, activation of the Na+-H+ exchanger which has been implicated in cell-cycle activation.