Gol-Winkler R
Clin Endocrinol Metab. 1986 Feb;15(1):99-115. doi: 10.1016/s0300-595x(86)80044-5.
Polypeptide growth factors form a class of regulatory molecules which exert their effects by binding to specific receptors present on the cell surface. Most of the time the exact role of these factors in the healthy body is unknown. Some, like PDGF and TGF beta, seem to be involved in wound healing. Others, like EGF, promote epithelial cell growth and differentiation. The site of synthesis of most polypeptide growth factors is unknown. Their target can be identified by detecting the cells which present the specific receptors at their surface. It is though that polypeptide growth factors have a paracrine mode of action. Many different cancerous cells produce polypeptide growth factors and the appropriate receptors. Thus, they are able to stimulate their own growth in an autocrine fashion. Recently, some polypeptide growth factors and receptor genes or cDNAs have been molecularly cloned. Growth factor genes and messengers are much more complex than would be expected from the size of the polypeptide. Some cDNAs have been introduced into bacterial expression vectors and large amounts of the factors have been produced by bacteria. New tools, such as molecular probes and specific antibodies, are thus now available to investigate the production of the growth factors and their receptors. The same tools will facilitate the identification and understanding of the molecular mechanism whereby cancerous cells produce the growth factors and the appropriate receptors simultaneously. The importance of growth factors and receptors in cancer is stressed by the finding that three oncogenes are in fact the genes coding for one growth factor and two receptors. Finally, the molecular probes and the specific antibodies raised against these molecules can be used to identify precisely the growth factor(s) and receptor(s) produced abnormally in cancers. Antibodies that inhibit specifically the interaction of this very growth factor with its receptor could then be developed, thus allowing human tumour cell growth to be controlled.
多肽生长因子构成一类调节分子,它们通过与细胞表面存在的特定受体结合来发挥作用。大多数情况下,这些因子在健康机体中的确切作用尚不清楚。有些因子,如血小板衍生生长因子(PDGF)和转化生长因子β(TGFβ),似乎参与伤口愈合。其他一些因子,如表皮生长因子(EGF),则促进上皮细胞的生长和分化。大多数多肽生长因子的合成部位尚不清楚。它们的靶细胞可通过检测表面呈现特定受体的细胞来确定。据认为,多肽生长因子具有旁分泌作用模式。许多不同的癌细胞会产生多肽生长因子和相应的受体。因此,它们能够以自分泌方式刺激自身生长。最近,一些多肽生长因子及其受体基因或cDNA已被分子克隆。生长因子基因和信使比根据多肽大小所预期的要复杂得多。一些cDNA已被引入细菌表达载体,细菌已大量生产这些因子。因此,现在有了新的工具,如分子探针和特异性抗体,可用于研究生长因子及其受体的产生。同样的工具将有助于识别和理解癌细胞同时产生生长因子和相应受体的分子机制。发现三个癌基因实际上是编码一种生长因子和两种受体的基因,这突出了生长因子和受体在癌症中的重要性。最后,针对这些分子产生的分子探针和特异性抗体可用于精确鉴定癌症中异常产生的生长因子和受体。然后可以开发能特异性抑制这种生长因子与其受体相互作用的抗体,从而控制人类肿瘤细胞的生长。