Moses H L, Coffey R J, Leof E B, Lyons R M, Keski-Oja J
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37322.
J Cell Physiol Suppl. 1987;Suppl 5:1-7. doi: 10.1002/jcp.1041330403.
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 proliferative potential and thereby contribute to the neoplastic phenotype.
已纯化并充分鉴定出两种转化生长因子（TGF），即TGFα和TGFβ。TGFα是一种5.6千道尔顿的单链分子，与表皮生长因子（EGF）具有序列同源性，能与EGF受体结合，其生物学效应与EGF非常相似。TGFβ在分子结构和生物学活性上与TGFα不同，有其自身特定的细胞表面受体。TGFβ是由12.5千道尔顿亚基组成的25千道尔顿同二聚体，与TGFα无序列同源性。TGFβ是一种由多种细胞类型以无活性形式产生的高度普遍存在的分子。大多数细胞都有TGFβ受体，这表明TGFβ作用的一个主要调节步骤是通过激活无活性形式。迄今为止，仅在成纤维细胞中观察到TGFβ的生长刺激作用。在至少一种情况下，有证据表明TGFβ在成纤维细胞中的刺激作用是间接的，通过诱导c-sis和血小板衍生生长因子（PDGF）样物质的自分泌刺激来实现。TGFβ在体外抑制大多数测试细胞类型的增殖，包括正常上皮细胞。因此，TGFβ主要是一种生长抑制剂，而非经典的生长因子。成纤维细胞中内源性TGFβ的自分泌刺激增加或上皮细胞（或其他通常受TGFβ抑制的细胞）中抑制作用降低，可能导致增殖潜能增加，从而促成肿瘤表型。
