The p53 paradox in the pathogenesis of tumor progression.
Recent evidence suggests that the p53 molecule appears in two different forms: the mutant p53 that stimulates tumor progression, and wild type p53 that inhibits tumor progression. In addition, it has been established that tumor necrosis factor-alpha (TNF-alpha) can activate the expression of wild type p53 in concert with the nuclear transcription factor, NF-kappa B. Both TNF-alpha and NF-kappa B are also involved in the stimulation of the pathway that leads to the expression of major histocompatibility complex (MHC) class I molecules and, hence, antigen presentation to the T cells. In this paper we shall advance the hypothesis that: (i) TNF-alpha indirectly controls immune surveillance; and (ii) TNF-alpha controls DNA repair and tumor suppression through the regulation of wild type p53. Thus, it is hypothesized that elevated TNF-alpha is primarily responsible for promoting tumor progression.
Medical Research Unit, University of Wollongong, New South Wales, Australia.
R J
RJ
Holden
P A
PA
Mooney
D018450:Disease Progression; D016158:Genes, p53; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53