Stochastic Modeling of Energy Balance in MCF-7 Breast Cancer Cells Taking Transposon Activity and Different Methylation States into Account

Abstract

Mobile genetic elements (transposons) demonstrate increased activity in cancer cells. One possible anticancer strategy is the use of the energy costs associated with abnormal activity of mobile elements to create conditions of energy starvation in the cell and the associated launch of the cell death program. A stochastic model of the energy balance in the cell population is proposed in this work, taking the energy costs of retrotransposition of mobile elements LINE-1 and SINE into account. The parameter values in the model were obtained from literature data and new experimental measurements of the ATP level in MCF-7 cells under normal conditions and under hypomethylation conditions. As a result of numerical stochastic modeling, distributions of the variables in the model were constructed, representing the numbers of mRNA molecules and proteins involved in the main energy-consuming cellular processes, as well as the number of active LINE-1 and SINE retrotransposons in the genome. The distributions of energy expenditures by major cellular processes under steady-state conditions were calculated. It is shown that low energy expenditures associated with retrotransposition of mobile elements under normal conditions increase significantly when the model parameters are perturbed. These results can be used to implement practical scenarios of influence on the energy-mediated initiation of cell death programs in cancer cells through the activation of mobile elements.