TRANSIENT EFFECT OF EPIDERMAL GROWTH-FACTOR ON THE MOTILITY OF AN IMMORTALIZED MAMMARY EPITHELIAL-CELL LINE

The effects of growth factors on epithelial cell motility and dispersi on have been examined on an immortalized human mammary epithelial cell line, the 184A1 nontumorigenic cell line. Among all the molecules tes ted, epidermal growth factor (EGF) and transforming growth factor-alph a (TGF-alpha) were demonstrated to stimulate an increase in mammary ep ithelial cell motility and wound closure that was associated with a mo rphological transformation of the cells and was accompanied by modific ations in cell-cell and cell-substrate adhesion systems. The EGF-induc ed increase in cell motility and monolayer wound closure occurred over a 24 hour period and was not dependent on an increase in cell number. The effect of EGF was abolished by inhibiting alpha2 integrins with s pecific antibodies, indicating that part of the mechanism for the incr ease in cell motility and accelerated wound closure depends on alpha2 integrin functional expression. After 72 hours of exposure to EGF, the EGF-induced alterations in cell morphology, motility and cell adhesio n systems underwent a spontaneous reversion that was correlated with a 10-fold reduction in the number of EGF receptors. The ability to regu late the scattering response induced by growth factors might be an imp ortant feature distinguishing normal epithelial cells from their tumor al counterparts.