Mummery C L, van der Saag P T, de Laat S W
J Cell Biochem. 1983;21(1):63-75. doi: 10.1002/jcb.240210108.
Mouse neuroblastoma cells (clone N1E-115) differentiate in culture upon withdrawal of serum growth factors and acquire the characteristics of neurons. We have shown tht exponentially growing N1E-115 cells possess functional epidermal growth factor (EGF) receptors but that the capacity for binding EGF and for stimulation of DNA synthesis is lost as the cells differentiate. Furthermore, in exponentially growing cells, EGF induces a rapid increase in amiloride-sensitive Na+ influx, followed by stimulation of the (Na+-K+)ATPase, indicating that activation of the Na+/H+ exchange mechanism in N1E-115 cells [1] may be induced by EGF. The ionic response is also lost during differentiation, but we have shown that the stimulation of both Na+ and K+ influx is directly proportional to the number of occupied receptors in all cells whether exponentially growing or differentiating, thus only indirectly dependent on the external EGF concentration. The linearity of the relationships indicates that there is no rate-limiting step between EGF binding and the ionic response. Our data would suggest that as neuroblastoma cells differentiate and acquire neuronal properties, their ability to respond to mitogens, both biologically and in the activation of cation transport processes, progressively decreases owing to the loss of the appropriate receptors.
小鼠神经母细胞瘤细胞（克隆N1E - 115）在血清生长因子撤除后于培养中发生分化，并获得神经元的特性。我们已经表明，指数生长的N1E - 115细胞拥有功能性表皮生长因子（EGF）受体，但随着细胞分化，结合EGF以及刺激DNA合成的能力丧失。此外，在指数生长的细胞中，EGF诱导amiloride敏感的Na⁺内流迅速增加，随后刺激（Na⁺ - K⁺）ATP酶，这表明N1E - 115细胞中Na⁺/H⁺交换机制的激活[1]可能由EGF诱导。离子反应在分化过程中也会丧失，但我们已经表明，无论是指数生长还是分化的所有细胞中，Na⁺和K⁺内流的刺激都与被占据受体的数量成正比，因此仅间接依赖于外部EGF浓度。这种关系的线性表明在EGF结合和离子反应之间不存在限速步骤。我们的数据表明，随着神经母细胞瘤细胞分化并获得神经元特性，由于适当受体的丧失，它们对有丝分裂原的生物学反应能力以及阳离子转运过程激活的能力逐渐下降。
