Transforming growth factor β regulation of cell proliferation

Two types of transforming growth factors (TGF) have been purified and well characterized, TGFα and TGFβ. TGFα is a 5.6 kD single chain molecule that shows sequence homology to epidermal growth factor (EGF), binds to the EGF receptor, and has biological effects very similar to those of EGF. TGFβ is different from TGFα in its molecular structure and biological activity, and has its own specific cell surface receptor. TGFβ is a 25 kD homodimer of 12.5 kD subunits that shows no sequence homology to TGFα. TGFβ is a highly ubiquitous molecule produced by a variety of cell types in an inactive form. Most cells have receptors for TGFβ, suggesting that a major regulatory step in TGFβ action is through activation of the inactive form. Growth stimulatory effects with TGFβ have been observed so far only in fibroblastic cells. In at least one circumstance, there is evidence that the stimulatory effects of TGFβ in fibroblastic cells is indirect through induction of c‐sis and autocrine stimulation by platelet‐derived growth factor (PDGF)‐like material. TGFβ inhibits in vitro proliferation of most cell types tested, including normal epithelial cells. Thus TGFβ is primarily a growth inhibitor and not a classical growth factor. Increased autocrine stimulation by endogenous TGFβ in fibroblastic cells or decreased inhibitory effects in epithelial cells (or other cells normally inhibited by TGFβ) could lead to an increased proliferative potential and thereby contribute to the neoplastic phenotype.