??53 gene Mutation and MDR Thecancer cell transformation andprogression is the most common changes is mutation of the TP53tumor in the suppressor gene 112–126. The normal situation theTP53 gene istriggered  in response to various cell harmless factors; inthe meantime, the wild type of p53 protein is synthesized, which leads to astop of the cell cycle and the apoptotic entering apoptosis occure 115, 116.In abnormalcells conditions for damaged DNA reparation, otherwise cells areremoved from the population. Cells that lacksnormal p53 are resistant to apoptosis induction 117. Thep53 mutagenic protein demonstrates the propertiesof an oncogene, which results in the startingof DNA replication in cells on the damaged matrix and development of malignanttransformation 118, 119. Therefore, tumor cells withmutant ??53 are resistant to the action of alteration factors104, 120. The stromalcells of epithelial cancer cells,especially, fibroblasts with normal gene?53, are capable to  and secrete tumor inhibitingfactors 121, 122. Likethat factors causing the wild type of p53 are acombination of agents that cause DNA damage indifferent ways, for example, by changing the redox-potential orthe nucleotide pool in the cell, thatleads to destructthe mitotic spindle of cell separation 115, 123.

Due to this fact,  cancer cells with themutant ?53 are resistant to treatmentwith different mechanism of action (for instance, to cisplatin and5-fluorouracil) 104. Variousfacts proving that the p53 protein helpin regulation of ABCB1 action. It has been noted that the wild type of p53suppresses and the mutant p53s protein increasesABCB1 activity 120. Inaddition, when studying MDR of rhabdomyosarcoma andneuroblastoma cell lines, it has been discoveredthat p53 is a majorinhibitor of P-glycoprotein andABCC1 (MRP1) functions andwhen suggestMDR of prostate cancer, the correlation between adecrease in the degree of tumor differentiation anda rise in MRP1 expression has been identified. Acombination of these two mechanisms led to development of tumor resistanceto doxorubicin and vinblastine 124, 125.

 Therefore, the strategy forreducing or preventing MDR may be thefunctional recovery of the wild type of p53  .itmay also help increase sensitization of cancer cellsto anti-cancerchemtherapy115, 116, 126, 127.


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