Transforming growth factors and control of neoplastic cell growth

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Abstract
Transforming growth factors (TGFs) are peptides that affect the growth and phenotypic of cultured cells and bring about in nonmalignant fibroblastic cells phenotypic properties that resemble those of malignant cells. Two types of TGFs have been well characterized. One of these, TGFβ, is related to epidermal growth factor (EGF) and binds to the EGF receptor, whereas the other. TGFβ, is not structurally or functionally related to TGFβ or EGF and mediates its effects via distinct receptors. TGFβ is produced by a variety of normal and malignant cells. Depending upon the assay system employed, TGFβ has both growth‐inhibitory and growth‐stimulating properties. Many of the mitogenic effects of TGFβ are probably an indirect result of the activation of certain growth factor genes in the target cell. The ubiquitous nature of the TGFβ receptor and the production of TGFβ in a latent form by most cultured cells suggests that the differing cellular responses to TGFβ are regulated either by events involved in the activation of the factor or by postreceptor mechanisms. The combined effects of TGFβ with other growth factors or inhibitors evidently play a central role in the control of normal and malignant cellular growth as well as in cell differentiation and morphogenesis. Since transforming growth factor as a concept has partially proven misleading and insufficient, there is a need to find a new nomenclature for these regulators of cellular growth and differentiation.