TRANSFORMING GROWTH-FACTOR BETA-REGULATION OF CELL-PROLIFERATION
TRANSFORMING GROWTH-FACTOR BETA-REGULATION OF CELL-PROLIFERATION
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DOI：
10.1002/jcp.1041330403
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发表时间：
1987-01-01
影响因子：
5.6
通讯作者：
KESKIOJA, J
中科院分区：
文献类型：
--
作者：
MOSES, HL;COFFEY, RJ;KESKIOJA, J
两种类型的转化生长因子（TGF）已被纯化和充分表征，TGFα和TGFβ。TGFα是一种5.6 kD的单链分子，与表皮生长因子（EGF）具有序列同源性，与EGF受体结合，具有与EGF非常相似的生物学作用。TGFβ在分子结构和生物学活性上与TGFα不同，有自己特异的细胞表面受体。TGFβ是12.5 kD亚基的25 kD同源二聚体，与TGFα没有序列同源性。TGFβ是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。大多数细胞具有TGFβ受体，表明TGFβ作用的主要调节步骤是通过激活非活性形式。迄今为止，仅在成纤维细胞中观察到TGFβ的生长刺激作用。至少在一种情况下，有证据表明TGFβ在成纤维细胞中的刺激作用是间接的，通过诱导血小板衍生生长因子（PDGF）样物质的c-sisand自分泌刺激。TGFβ 1在大多数测试的细胞类型的体外增殖中，包括正常上皮细胞。因此，TGFβ主要是生长抑制剂，而不是经典的生长因子。成纤维细胞中内源性TGFβ的自分泌刺激增加或上皮细胞（或通常受TGFβ抑制的其他细胞）中抑制作用降低可能导致增殖潜力增加，从而导致肿瘤表型。
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‐sisand autocrine stimulation by platelet‐derived growth factor (PDGF)‐like material. TGFβ inhibitsin vitroproliferation 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.