Mechanism of homeostatic regulation of tissue growth and reversion of transformed cells to nonmalignancy: a yin-yang problem.
The regulation of coordinated cell growth and the development of malignancy are phenomena that are too complex to be accommodated in a narrow frame. However, on the basis of about 30 years experience with interferon and the analysis of the literature presently available, it can be suggested that: (i) normal growth is discontinuous, promoted by various growth factors; (ii) its development is downregulated by a great variety of alpha/beta interferons, which are easy to detect in rapidly growing tissues during the fetal period. Arrest of the cells in interphase could promote the expression of genetically programmed differentiation; (iii) recycling of growth is obtained by sarcolectins able to downregulate the cellular effects of interferons and to relaunch cell multiplication. To maintain harmonious growth, the synthesis and the effect of these proteins have to be in equilibrium. In transformed cells, after prolonged treatment with IFN (acting as an antioncogene), v-mos, beta interferon, and sarcolectin are continuously expressed and stay in balance. This could explain in part the stable reversion to nonmalignancy, under conditions that are reminiscent of the ancestral "Yin-Yang" principle. The review presented here is restricted to the inteferon system, whose importance in coordinated growth regulation is presently poorly defined. It can be judged, however, probably significant because of the great number of alpha isoforms existing in addition to IFN-beta, which are responsible for the activation of a number of more or less defined secondary proteins; each of these could have a more specific biological role as regards the great number of growth factors and promoters.
Université René Descartes, U43 INSERM, Hôpital St. Vincent de Paul, Paris, France.
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D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D006131:Growth Inhibitors / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007372:Interferons / Q000502:physiology; D009857:Oncogenes / Q000502:physiology; D011519:Proto-Oncogenes / Q000502:physiology
D006131:Growth Inhibitors; D006133:Growth Substances; D007372:Interferons