The Regulate and Controlof Slug on P53-MDM2 System
|School||Hebei University of Technology|
|Keywords||p53 network slug tumor metastasis p53-mdm2-slug complex|
Cancer mortality in China over the past 30 years, an increase of 80%, it has become the first cause of death of Chinese residents. Cancer metastasis is an important issue in cancer research. Activation of the Slug will restore the ability of cell migration, Slug exist in a variety of malignant tumors were significantly increased, thus speculated that inhibition of Slug expression maybe have anti-tumor effect.According to the experimental facts that in normal cells, p53 up regulates MDM2 and forms a p53–MDM2–Slug complex that facilitates MDM2-mediated Slug degradation. which inhibit cancer cell metastasis.In this paper, mainly through the establishment of theoretical models, researches the situation in different MDM2 and p53 is to regulate the content of Slug and the Slug and its content network the number of negative feedback on the role of p53, when DNA is repaired completely, p53 back to normal cell level. The first is the establishment of the p53-MDM2-Slug theoretical model, and further use of the theoretical model for fixed-point stability analysis to identify the conditions for fixed-point downward, indicating that normal cells, the Slug and the p53-MDM2 interaction, can make the Slug and the p53-MDM2 remained low. Detailed calculation of the system, made by calculation and simulation results are compared with the experiment, the last relevant results obtained in normal cells, Slug, and p53-MDM2 interaction will make the Slug and p53-MDM2 oscillations remain at a low level.Concluded that: Slug changes to the network of p53-MDM2 oscillation of the impact of the oscillation amplitude can be smaller and the oscillation of the stable points lower; appropriate Slug content enables p53-MDM2-Slug complex degradation; find out to reduce the impact of cancer metastasis factors, including: accumulation of Slug, MDM2 dependent on the growth rate of p53 and the rate of MDM2 on the role of p53.