THE 27-KDA HEAT-SHOCK PROTEIN FACILITATES BASIC FIBROBLAST GROWTH-FACTOR RELEASE FROM ENDOTHELIAL-CELLS

Basic fibroblast growth factor is an important mitogenic and angiogeni c factor that stimulates endothelial cell growth and migration. This h ormone is not secreted via the classical vesicular pathway, and the id entification of intracellular proteins that facilitate its release rem ains lacking, Transfection and expression of the 27-kDa human heat sho ck protein in bovine arterial endothelial cells doubles the rate of es trogen-induced basic fibroblast growth factor secretion, preferentiall y inducing the release of high molecular weight forms of the hormone. The secreted basic fibroblast growth factor is mitogenic to breast ade nocarcinoma cells cultured in the conditioned medium obtained from the transfected endothelial cells, In contrast, decreasing the level of t he endogenous heat shock protein homolog with an antisense vector mark edly decreases basic fibroblast growth factor release, Anti-heat shock protein or anti-basic fibroblast growth factor antibodies co-precipit ate both proteins from endothelial cell extracts, demonstrating a dire ct association between the two proteins. This interaction is likely to be an important step in the mechanism of basic fibroblast growth fact or secretion.