Nilsen-Hamilton M
Department of Biochemistry and Biophysics, Iowa State University, Ames 50011.
Curr Top Dev Biol. 1990;24:95-136.
TGF-beta stimulates the anchorage-dependent proliferation of some cells and inhibits the proliferation of others. Although the ability of TGF-beta to affect different cell types in opposite ways is puzzling, it may not reflect fundamental differences in the initial cellular responses to TGF-beta. Instead, the different types of cellular responses may be because TGF-beta initiates a number of changes in all responsive cells, some of which may lead to proliferation and others, to proliferative arrest. Depending on the individual responses of specific cell types and on the environment of the cells, the balance of the effects of these changes could lead to cellular proliferation or inhibition of proliferation. This hypothesis is discussed in more detail below, with specific reference to the effects of TGF-beta on the expression of genes encoding proteases, protease inhibitors, ECM components, and growth and differentiation factors. TGF-beta also promotes the anchorage-independent growth of some cells in soft agar, but inhibits the anchorage-independent proliferation of some tumor cells. In stimulating proliferation TGF-beta often acts synergistically with EGF, FGF, TGF-alpha, or PDGF. The observed increase in soft agar growth in response to TGF-beta could be explained by a model which proposes that TGF-beta stimulates the accumulation of the ECM, which supports the action of the growth factors (e.g., EGF, TGF-alpha, PDGF, and FGF) that directly stimulate cellular proliferation. The ability of TGF-beta to inhibit the proliferation of some cells in soft agar again reminds us that the mechanism of action of this growth factor is not readily described by a single model. Although its proven ability to regulate the expression of genes that encode proteins that constitute or modify the ECM ensures TGF-beta a role in ECM remodeling, the complexity of the multiple cellular responses to this growth factor suggest that there is another aspect of the function of this growth factor. Perhaps the observations that TGF-beta stimulates the production of FSH and PDGF are the tip of the iceberg. If TGF-beta regulates a subset of genes that encode growth factors and their receptors, then this could help to explain the many and varied cellular responses to TGF-beta. By regulating genes encoding other hormones and growth factors, TGF-beta might be a "master morphogen" during development and orchestrate the local elaboration of growth factors and hormones by individual cell types.
转化生长因子-β（TGF-β）可刺激某些细胞的贴壁依赖性增殖，同时抑制其他细胞的增殖。尽管TGF-β以相反方式影响不同细胞类型的能力令人费解，但这可能并不反映细胞对TGF-β初始反应的根本差异。相反，不同类型的细胞反应可能是因为TGF-β在所有反应性细胞中引发了许多变化，其中一些变化可能导致增殖，而其他变化则导致增殖停滞。根据特定细胞类型的个体反应以及细胞所处的环境，这些变化的影响平衡可能导致细胞增殖或增殖抑制。下面将更详细地讨论这一假说，特别提及TGF-β对编码蛋白酶、蛋白酶抑制剂、细胞外基质（ECM）成分以及生长和分化因子的基因表达的影响。TGF-β还可促进某些细胞在软琼脂中的非贴壁依赖性生长，但抑制某些肿瘤细胞的非贴壁依赖性增殖。在刺激增殖方面，TGF-β通常与表皮生长因子（EGF）、成纤维细胞生长因子（FGF）、转化生长因子-α（TGF-α）或血小板衍生生长因子（PDGF）协同作用。观察到的TGF-β诱导软琼脂中生长增加的现象，可以用一个模型来解释，该模型提出TGF-β刺激ECM的积累，而ECM支持直接刺激细胞增殖的生长因子（如EGF、TGF-α、PDGF和FGF）的作用。TGF-β抑制软琼脂中某些细胞增殖的能力再次提醒我们，这种生长因子的作用机制很难用单一模型来描述。尽管TGF-β调节编码构成或修饰ECM的蛋白质的基因表达的能力已得到证实，这确保了TGF-β在ECM重塑中发挥作用，但对这种生长因子的多种细胞反应的复杂性表明，该生长因子的功能还有另一个方面。也许TGF-β刺激促卵泡激素（FSH）和PDGF产生的观察结果只是冰山一角。如果TGF-β调节编码生长因子及其受体的一部分基因，那么这有助于解释对TGF-β的众多不同细胞反应。通过调节编码其他激素和生长因子的基因，TGF-β可能在发育过程中是一种“主要形态发生素”，并协调个体细胞类型对生长因子和激素的局部精细调节。
