P53 tumour suppressor gene

Harris CC. p53 Tumour suppressor gene At the crossroads of molecular carcinogenesis, molecular epidemiology and cancer risk assessment. Environ Health Persp 1996 104 435. 

Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature 19991 351 453-56. 

Franklin, T.M., J.S. Lee, A. Kohler and J.K. Chipman. Analysis of mutations in the p53 tumour suppressor gene and Ki- and Ha -ras proto-oncogenes in hepatic tumours of European flounder (Platichthys flesus). Mar. Environ. Res. 50 251-255, 2000. 

A specific mutation in the p53 tumour suppressor gene has been detected in 10-70% of HCCs from areas of high AFBi exposure and is absent from HCCs from areas with negligible AFBi exposure [28-30]. Support for the implication that the mutation, a G- T transversion at the third base of codon 249, is caused by exposure to aflatoxin has come from in vitro studies. Aflatoxin exposure in bacteria almost exclusively causes G—transversions [31] and the aflatoxin-epoxide has been shown to bind to codon 249 of p53 in vitro [32]. Moreover, human... 

Kay C, Jeyendran RS, Coulam CB. 2006. p53 tumour suppressor gene polymorphism is associated with recurrent implantation failure. Reprod Biomed Online 13(4) 492-496. 

Letzel S, Drexler H, Lehnert G (1992) Teer-induzierte Praekan-zerosen und Malignome der Haut bei Beschaeftigten einer Teer-Raffinerie. Dermatosen 40 94-101 Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351 453-456 Millard LG (1986) Multiple pigmented papular basal cell carcinomas a new pattern of industrial tar induced skin tumours. Br J Ind Med 43 143-136... 

PNA probes having two fluorophores have been used for detection of DNA and RNA, exemplified by the dual colour imaging of two mRNA targets in influenza MINI infected cells. PNA has been modified with a quinone methide for the site-specific alleviation of complementaiy DNA. " A PNA probe has been used in a label-free electrochemical sensor with picomolar sensitivity for profiling the methylation states of the p53 tumour suppressor gene. A lysine-tagged PNA oligomer has been developed for use as an amperometric sensor. ... 

S100A2 encoding cDNA was first identified as a novel tumour suppressor gene. S100A2 interacts in a Ca2+-dependent manner with the tumour suppressor p53 and activates its transcriptional activity. S100A2 was shown to interact with the same p53 binding site as S100B. 

Figure 21.11 Role of p53 as a tumour suppressor gene. p53 induces a cell with damaged DNA either to initiate apoptosis, or arrest the cell cycle, to give time for damaged DNA to be repaired. Damage can be, for example, a mutation, DNA strand breakage or chromosomal rearrangement.

In many chronic inflammatory diseases, angiogenesis can be identified in the inflamed lesions. For example, in rheumatoid arthritis extensive neovascularization is present in the inflamed synovium where it is one of the earliest histopathological findings [36]. Since in RA synoviocytes exhibit characteristics of tumour cells, including somatic mutations in key regulatory genes such as H-ras and the p53 tumour suppressor, RA can be viewed as a multicentric tumour-like mass that invades and destroys its local environment [37]. Concurrent increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis. 

An alternative anti-cancer strategy entails insertion of a copy of a tumour suppressor gene into cancer cells. For example, a deficiency in one such gene product, p53, has been directly implicated in the development of various human cancers. It has been shown in vitro that insertion of a p53 gene into p53-deficient tumour cells induces the death of such cells. A weakness of such an approach, however, is that 100% of the transformed cells would have to be successfully treated to fully cure the cancer. 

Hypermethylation of the tumour-suppressor gene, p53, has been found in cancerous mice. Methylation of DNA has been assumed to be irreversible and the irreversibility has been linked to a possible mutagenic role of methylation in cancer. However, recently a mammalian demethylating enzyme has been identified, but how methylation patterns and gene expression are exactly related is not yet clear (Chapter 10). However, it can be expected that we shall learn more about the role of methylation of DNA in cancer in the future. 

Tumour-suppressor gene The tumour-suppressor gene p53 is located on chromosome 17. Noxae may cause mutations of this gene, which results in the loss of its suppressor effect. (6, 126) An autosomal dominant mutation of p53 is also encountered in humans, so that a tumour can develop during adolescence, the so-called Li-Fraumeni syndrome. 

PCR is also being used to screen mutations in tumour suppressor genes such as the retinoblastoma and the p53 genes. 

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