Transforming growth factor ? regulation of cell proliferation

作者：Harold L. Moses, Robert J. Coffey, Edward B. Leof, Russette M. Lyons, Jorma Keski‐Oja · 发表于：Journal of Cellular Physiology · 年份：1987 · DOI：10.1002/jcp.1041330403 · 被引用次数：155 · 研究领域：TGF-β signaling in diseases、Growth Hormone and Insulin-like Growth Factors、Liver physiology and pathology

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