Possible positive autocrine feedback in the prereplicative phase of human fibroblasts

Abstract

The growth of normal diploid fibroblasts is generally thought to be tightly controlled by exogenous growth factors such as platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). Subversion of a growth factor pathway at a regulatory point is considered to be a key event in neoplastic transformation and tumorigenesis¹. Thus, simian sarcoma virus has acquired the gene encoding the B-chain of PDGF^2–4 and there is direct experimental proof that SSV-transformation is mediated by a PDGF-like growth factor⁵. There is accumulating evidence that PDGF-like molecules are also synthesized and released by certain normal cells^6–3, suggesting an important role of cellularly produced PDGF in development and tissue regeneration. We now present evidence that a transient expression of the gene encoding the PDGF A-chain, and the synthesis and release of functional A-chain homodimers, is an early event in the prereplicative phase of normal human foreskin fibroblasts exposed to PDGF or EGF. Since these cells are PDGF-responsive, the results imply the existence of a positive autocrine signal that may serve as an amplifier of the mitogenic response under certain conditions.