Insulin-like growth factor binding protein-3 does not mediate the interferon-dependent suppression of human ectocervical epithelial cell proliferation

Interferon is a potential therapeutic agent for the treatment of cervical c ancer. In the present study we examine the role of IFN gamma as a regulator of proliferation and production of IGFBP-3 expression in ectocervical epit helial cells. ECE16-1 cells are a model for studying early human papillomav irus-dependent cervical disease. IFN gamma produces a concentration-depende nt inhibition of ECE16-1 cell proliferation that is associated with an incr ease in insulin-like growth factor binding protein-3 level. Growth suppress ion and IGFBP-3 increase is maximal at concentrations of IFN gamma greater than or equal to 0.75 ng/ml. The increased IGFBP-3 expression is mediated v ia an increase in IGFBP-3 encoding mRNA. In contrast, IFN gamma inhibits pr oliferation of CaSki and SiHa cells, but IGFBP-3 is barely detectable and l evels are not regulated by IFN gamma. These results suggest that the IFN ga mma-dependent suppression of CaSki and SiHa cell proliferation is not media ted by secreted IGFBP-3. This result was confirmed when vector-mediated ove rexpression of immunoreactive IGFBP-3 in SiHa and CaSki cells did not consi stently result in reduced cell proliferation rate.