TRANSFECTION OF THE HUMAN IGFBP-3 GENE INTO BALB C FIBROBLASTS - A MODEL FOR THE CELLULAR FUNCTIONS OF IGFBPS/

The insulin-like growth factors (IGFs) are potent mitogens with both e ndocrine and autocrine-paracrine effects on cell growth. The insulin-l ike growth factor binding proteins (IGFBPs) are found in many human bi ological fluids and in the conditioned media of many cell cultures. Th ese molecules are ontogenically and hormonally regulated. Nevertheless , the biological role(s) of the IGFBPs remain controversial. Both inhi bitory and stimulatory effects of IGFBPs on cell growth have been sugg ested. In order to evaluate the actions of endogenously produced IGFBP s on cell growth, we have constructed a mammalian expression vector co ntaining the hIGFBP-3 cDNA, and transfected the murine Balb/c cell lin e. The IGFBP-3 transfected Balb/c cells (Tx-BP-3) expressed readily de tectable amounts of hIGFBP-3 protein and its mRNA. Growth of Tx-BP-3 i n serum containing media was significantly slower, compared with contr ol plasmid-transfected cells (Tx-P) grown under identical conditions. Fully confluent Tx-BP-3 cells arrested their growth at a cell density that was lower than did Tx-P cells. When transfected cells were grown in insulin-containing media, growth rates of the IGFBP-3 transfected c ells were not restored to those observed in control plasmid-transfecte d cells. These results suggest that in this model, the expression of e ndogenous IGFBP-3 has an inhibitory effect on cell growth.