Insulin-like growth factor binding protein-4 gene expression is induced by transfection of gap junction connexin43 gene in a C6 glioma cell line.

When C6 glioma cells are stably transfected with a connexin43 cDNA and the gene overexpressed, the rate of cellular proliferation is decreased. To determine if this phenomenon is related to alterations in IGFBP synthesis, we have compared the conditioned media of primary rat astroglia, C6, clones Cx43-13 (high expresser of the transfected connexin43 gene), and Cx43-12 and Cx43-14 (intermediate expressers). Primary astroglia produced IGFBP-2 (M(r) 34 K) and IGFBP-3 (40-45 K). C6 cells synthesized high levels of IGFBP-3 and low levels of IGFBP-2, and a 24 K IGFBP (IGFBP-4). Cx43-13 cells did not synthesize IGFBP-3, but produced low levels of IGFBP-2 and high levels of IGFBP-4. Cx43-12 and Cx43-14 secreted IGFBP profiles similar to the parent C6 line, but with reduced levels of IGFBP-2. Northern analysis showed the changes in IGFBPs in the conditioned media to be correlated with alterations in stable mRNA levels. IGFBP-4, a inhibitor of IGF biological action, was produced in greater quantities by the slowly proliferating Cx43-13 cells. Alterations in IGFBP-4 synthesis may be responsible, at least in part, for the reduced proliferative capacity in cells with abundant connexin43.