??53 gene Mutation and MDR

The
cancer cell transformation and
progression is the most common changes is mutation of the TP53
tumor in the suppressor gene 112–126. The normal situation the
TP53 gene is
triggered  in response to various cell harmless
 factors; in
the meantime, the wild type of p53 protein is synthesized, which leads to a
stop of the cell cycle and the apoptotic entering apoptosis occure 115, 116.
In abnormal
cells conditions for damaged DNA reparation, otherwise cells are
removed from the population. Cells that lacks
normal p53 are resistant to apoptosis induction 117. The
p53 mutagenic protein demonstrates the properties
of an oncogene, which results in the starting
of DNA replication in cells on the damaged matrix and
 development of malignant
transformation 118, 119. Therefore, tumor cells with
mutant ??53 are resistant to the action of alteration factors
104, 120. The stromal
cells of epithelial cancer cells,
especially, fibroblasts with normal gene
?53, are capable to  and secrete tumor inhibiting
factors 121, 122. Like
that factors causing the wild type of p53 are a
combination of agents that cause DNA damage in
different ways, for example, by changing the redox-potential or
the nucleotide pool in the cell, that
leads to destruct
the mitotic spindle of cell separation 115, 123. Due to this fact,  cancer cells with the
mutant ?53 are resistant to treatment
with different mechanism of action (for instance, to cisplatin and
5-fluorouracil) 104. Various
facts proving that the p53 protein help
in regulation of ABCB1 action. It has been noted that the wild type of p53
suppresses and the mutant p53s protein increases
ABCB1 activity 120. In
addition, when studying MDR of rhabdomyosarcoma and
neuroblastoma cell lines, it has been discovered
that p53 is a major
inhibitor of P-glycoprotein and
ABCC1 (MRP1) functions and
when suggest
MDR of prostate cancer
, the correlation between a
decrease in the degree of tumor differentiation and
a rise in MRP1 expression has been identified. A
combination of these two mechanisms led to development of tumor resistance
to doxorubicin and vinblastine 124, 125.  Therefore, the strategy for
reducing or preventing MDR may be the
functional recovery of the wild type of p53  .it
may also help increase sensitization of cancer cells
to anti-cancer
chemtherapy
115, 116, 126, 127.

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