A mathematical model of P53 gene regulatory networks under radiotherapy.
P53, a vital anticancer gene, controls the transcription and translation of a series of genes, and implement the cell cycle arrest and cell apoptosis by regulating their complicated signal pathways. Under radiotherapy, cell can trigger internal self-defense mechanisms in fighting against genome stresses induced by acute ion radiation (IR). To simulate the investigating of cellular responding acute IR at single cell level further, we propose a model of P53 gene regulatory networks under radiotherapy. Our model can successfully implement the kinetics of double strand breaks (DSBs) generating and their repair, ataxia telangiectasia mutated (ATM) activation, as well as P53-MDM2 feedback regulating. By comparing simulations under different IR dose, we can try to find the optimal strategy in controlling of IR dose and therapy time, and provide some theoretical analysis to obtain much better outcome of radiotherapy further.
Qi
J P
JP
College of Information Sciences & Technology, Donghua University, Shanghai 201620, China. qipengkai@mail.dhu.edu.cn
Shao
S H
SH
Xie
Jinli
J
Zhu
Y
Y
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D005246:Feedback; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D049490:Systems Biology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases