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

Abstract

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.

Serum- and glucocorticoid-inducible kinase 1 in the regulation of renal and extrarenal potassium transport

“…, K ? , 2Cl -cotransporter in several cell types including skeletal muscle [88,89], vascular smooth muscle [90], liver [91], epithelial cells [92][93][94], fibroblasts [95][96][97], adipocytes [98] and erythrocytes [99][100][101][102]. The Na ?…”

Impaired expression and posttranslational processing of connexin43 and downregulation of gap junctional communication in neoplastic human prostate cells

“…1c,d). In another nonneoplastic human cell line, WI38 [21], all three forms of Cx43 were also seen (Fig. 2, lane 1) and correlated with its high cell communication abilities (data not shown).…”

CSF‐1 stimulates nucleoside transport in S1 macrophages

“…In mouse fibroblasts system A amino acid transport changes with the cell cycle, with a peak near the end of GI just prior to entering S phase (Leister et al, 1989). Insulin increases glucose transport in muscle tissue and has effects on Ca2+ and amino acid fluxes in muscle and other tissues (Klip et al, 1984;Tupper and Smith, 1985;Bettger and McKeehan, 19861, and CSF-1 stimulates coupling between hexose transport and hexokinase activity in rat and murine peritoneal macrophages (Rist et al, 1990).…”