Tumour-suppressor gene

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. 

Modifying lymphocytes in order to enhance their anti-tumour activity Modifying tumour cells to enhance their immunogenicity Inserting tumour suppressor genes into tumour cells... 

An oncogene has been compared with a car with a stuck accelerator the car moves even if you take your foot off the accelerator. However, the car will stop if the brake is pressed (this is the effect of the tumour suppressor gene). A mutation in or the loss of a tumour suppressor gene is analogous to a faulty brake, i.e. it no longer halts proliferation of the abnormal ceU (Vogelstein Kinzer, 2004). 

There are two classes of tumour suppressor genes gatekeeper genes and caretaker genes. If the activity of a... 

Loss of tumour suppressor activity leads to production of a tumour in a homozygous recessive manner. This means that both alleles must be mutated for loss of control of the cell cycle to be lost and uncontrolled proliferation to occur. At least 30 different tumour suppressor genes have been identified but the mechanisms of suppression will probably be different for each gene. The mechanisms for two are presented. 

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.

The Rb locus that is affected by the mutation, and that causes retinoblastoma, is a tumour suppressor gene. It encodes the Rb protein which is an inhibitor of transcription. The Rb protein controls the expression of three genes, which are essential for cell proliferation by forming a complex with, and thus inactivating, a transcription factor for these genes. These are ... 

Figure 21.19 Development of a secondary carcinoma from a normal epithelium by effects of activated genes, i.e. oncogenes, and inactive tumour suppressor genes. It is somatic mutations in four or five genes in a given cell plus hypomethylation changes in histones and chromatin stracture that are involved. It is the accumulation of these genetic alterations, not the sequence, that determines the progression to a tumour cell.

The sequence of events from mutations or damage to proto-oncogenes and leads to tumour suppressor genes, loss of development of cancer, with its metabolic disturbances and cachexia. Finally these changes can lead to... 

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. 

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

Stanley LA. Molecular aspects of chemical carcinogenesis The role of oncogenes and tumour suppressor genes. Toxicology 1995 96 173. 

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