Mutual interactions between p53 and growth factors in cancer.
The function of p53 tumour suppressor protein is determined by various intrinsic properties of the protein. The effect of p53 DNA-binding, and protein-protein interactions are determined by the conformation of the protein. Thus, p53 fulfils its role in cell cycle control and the onset of apoptotic cell death, which is altered when the wild-type p53 (wt-p53) conformation is changed due to mutation. This review focuses on the communal interactions of wt- and mutant p53 (m-p53) with growth factors and shows that m-p53 affects different cell biological functions that determine the malignant behaviour of cells. P53, for instance, affects the response of cells to growth factors and growth factor-withdrawal. Furthermore, p53 is involved in the expression of several growth factor- and growth factor receptor genes. These data suggest that restoration of the wt-p53 phenotype in tumour cells with m-53 might not only affect cell cycle control and apoptotic mechanisms but could also reduce autocrine growth and restore sensitivity to physiological growth inhibitors.
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
J G
JG
Asschert
E
E
Vellenga
S
S
De Jong
E G
EG
de Vries
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D016213:Cyclins / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000502:physiology; D006133:Growth Substances / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology*
D016213:Cyclins; D006131:Growth Inhibitors; D006133:Growth Substances; D017978:Receptors, Growth Factor; D016159:Tumor Suppressor Protein p53