Paci A, Ciarimboli G, Ferdeghini M
Istituto di Fisiologia Clinica, C.N.R., Pisa.
Minerva Med. 1994 Sep;85(9):467-90.
The processes of cellular proliferation and progressive acquisition of a specialized phenotype show a remarkable degree of coordination that involves both intracellular programming and intercellular communication. One of the major incentives for studying factors that regulate the processes of cellular proliferation and differentiation is the recognition of their potential contribution to tumorigenesis. In normal cells, stimulatory and inhibitory events are believed to be under the control of growth factors and growth inhibitory factors, which are known to be protooncogene products. Growth regulatory mechanisms usually involve the binding of a growth factor to a specific receptor on the cell surface, which then through an intracellular biochemical cascade leads to cell division. The cell regulation pathways initiated by growth factors may be subverted at several distinct levels in cancer cells. Studies of oncogenes have shown that they may function as abnormal growth factors or abnormal receptors, induce expression of potential signal regulators or encode proteins which modulate gene transcription. The purpose of the present paper is to examine the role of growth factors, growth factor receptors and intracellular proteins involved in signal transduction (with particular regard to the epidermal growth factor receptor system) in the control of normal growth and differentiation, and their contribution to transformation and tumorigenesis. We also review the classical theories of neoplasia and various other models. Chemical carcinogenesis and Vogelstein-Lane model are presented.
细胞增殖过程以及逐渐获得特定表型的过程展现出了高度的协调性,这涉及细胞内编程和细胞间通讯。研究调控细胞增殖和分化过程的因素的主要动机之一,是认识到它们对肿瘤发生的潜在作用。在正常细胞中,刺激和抑制事件被认为受生长因子和生长抑制因子的控制,而这些因子已知是原癌基因的产物。生长调节机制通常涉及生长因子与细胞表面特定受体的结合,然后通过细胞内生化级联反应导致细胞分裂。由生长因子启动的细胞调节途径在癌细胞中可能在几个不同层面被颠覆。对癌基因的研究表明,它们可能作为异常生长因子或异常受体发挥作用,诱导潜在信号调节因子的表达或编码调节基因转录的蛋白质。本文的目的是研究生长因子、生长因子受体以及参与信号转导的细胞内蛋白质(特别是表皮生长因子受体系统)在正常生长和分化控制中的作用,以及它们对转化和肿瘤发生的作用。我们还回顾了肿瘤形成的经典理论和各种其他模型。介绍了化学致癌作用和沃格尔斯坦 - 莱恩模型。