Epidermal growth factor suppresses insulin-like growth factor binding protein 3 levels in XXXX -immortalized cervical epithelial cells and thereby potentiates the effects of insulin-like growth factor 1.

@entity1 @entity2301 @entity5 @entity442 @entity281 @entity2533 @entity1799 @entity1082
@entity1 ectocervical epithelial cells are a primary target for @entity281 , which are strongly implicated as causative agents in the genesis of @entity5 . Growth factors have been implicated as agents that stimulate proliferation and enhance the possibility of malignant transformation. In the present study we utilize several @entity1082 ) @entity1799 -immortalized ectocervical epithelial cell lines to investigate the effects of epidermal growth factor (EGF) and insulin-like growth factor I ( @entity442 ) on cell proliferation and the production of IGF binding proteins (IGFBPs). ECE16-1 cells, an @entity1799 -immortalized/nontumorigenic cell line, maintained in defined medium, produce and release high levels of @entity2301 (38/42 kDa) as well as smaller amounts of a 24-kDa IGFBP. Supplementation of defined medium with EGF causes a dose-dependent increase in cell growth and a concomitant decrease in the levels of @entity2301 released into the culture medium. EGF suppression of @entity2301 is maintained even when EGF-stimulated cell growth is suppressed 67% due to the simultaneous presence of 3 ng/ml of @entity2533 , indicating that EGF suppression of @entity2301 levels is independent of EGF effects on cell growth. EGF suppression of @entity2301 production is correlated with a reduction in @entity2301 mRNA level. In the presence of EGF, the growth response of the cells to ng amounts of @entity442 is significantly enhanced. Moreover, the simultaneous presence of both EGF and @entity442 reduces the level of @entity2301 more efficiently than EGF alone. We also observe that the @entity2301 level is decreased and the 24-kDa IGFBP level is increased in @entity1799 -positive tumorigenic versus nontumorigenic cell lines. This is the first report of EGF acting as a positive regulator of @entity442 action via the IGFBPs. On the basis of these findings, we propose that EGF stimulates ECE16-1 cell growth via a dual-action mechanism by (a) stimulating growth directly via the EGF mitogenic pathway and (b) stimulating growth indirectly by reducing the levels of inhibitory IGFBPs and thereby potentiating the effects of @entity442 . In addition, the observation that more highly transformed cell types produce lower levels of @entity2301 and higher levels of 24-kDa IGFBP suggests that @entity5 cells in more @entity5 may have an altered response to @entity442 .
