The inverse relationship between maspin and p53 expression predicted by hypothesized p53 regulation of maspin transcription, or any other correlation between these 2 markers, is not demonstrated in MM cases, using either classic individual slide (P=0.20) or TMA (P=0.85) methods when cutoffs for both markers are set at 10% or greater of cells staining.
These studies suggest that compromise of either p53 or Rb pathways during melanocyte transformation leads to up-regulation of survivin expression in melanoma.
The association of the p53 Pro/Pro genotype with melanoma risk was strongest among women with light pigmentation, and with MC1R variants, with the joint risk categories having the highest overall risk.
Both p53 and the small molecular weight forms of p53 were aberrantly expressed between the nuclear and cytosolic fractions of melanoma cell lines, compared with normal fibroblasts.
This review summarises the current knowledge of alterations in these two pathways at G1/S transition and specifically the role of the key cell cycle regulatory proteins pRb, p16INK4a (p16), cyclin D1, p27Kip1 (p27), p53 and p21Waf1/Cip1 (p21) in the pathogenesis of melanoma.
Taken together, our data point to a clear need in human melanoma cell lines, as in its murine counterpart, to disrupt both RB and p53 pathways and recurrent mechanisms may play into the unique genetic vulnerabilities of this tumor type.
This article reviews p53 alterations (at the gene and protein levels) in melanocytic skin lesions and discusses the following points: (i) p53 alterations commence as early as at the stage of benign and dysplastic nevi; (ii) these alterations are frequent in melanomas, and gradually increase with their progression; (iii) there is no concordance between the frequent p53 protein expression and the rarity of both TP53 gene mutations in melanomas, and (iv) the entire p53 pathway is a more critical determinant of the fate of the melanocytic skin lesions than the status of the p53 protein or the gene itself.
Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells.
In conclusion, this study found some evidence that in subjects over 50, p53 Arg/Arg genotype is associated with increased risk of CM as compared to genotypes Arg/Pro or Pro/Pro.
In this study, we show that inhibition of p53 causes ubiquitination and down-regulation, through increased degradation, of the IGF-1R in human malignant melanoma cells.