In normal, untransformed cells, growth is a tightly regulated process, A single cell is capable of controlling its growth by integrating the input from both positive growthstimulating and negative growth-inhibiting signals. Unrestrained cell proliferation is the hallmark of carcinogenesis and arises as a consequence of aberrations in this normal growth control. The importance of such disturbed growth-regulating mechanisms is underscored by the observation that in vitro tumour cells were found to proliferate independently of exogenous growth factors. The apparent ability to be able to grow without mitogenic factors supported the earlier suggestion of Temin that growth of transformed cells may be caused by endogenous production of growth factors. This concept was later extended to the autoerine growth stimulation model. It has become generally accepted that genetic damage is a central event in the process of loss of growth control. Disturbances in the growth-regulating mechanisms by changes in the genes til at govern these processes, consequently enable cells to escape normal growth control. Genes, whose products contribute to uncontrolled growth, once they are genetically altered, can be classified as oncogenes and tumour suppressor genes. In the former category such genetic alterations give rise to a gain-of-function resulting in positive growth stimulation (e.g. by changes in growth factor-encoding genes), whereas in the latter growth-inhibiting properties are lost.

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R. Benner (Robbert)
Erasmus University Rotterdam
Dutch Cancer Society, B & L Systems (Maarssen, the Netherlands)
Erasmus MC: University Medical Center Rotterdam

Langerak, A.W. (1995, October 11). Regulation of PDGF chain and receptor expression in human malignant mesothelioma cell lines. Erasmus University Rotterdam. Retrieved from