Stochastic modelling of PTEN regulation in brain tumors: A model for glioblastoma multiforme

Math Biosci Eng. 2015 Oct;12(5):965-81. doi: 10.3934/mbe.2015.12.965.

Abstract

This work is the outcome of the partnership between the mathematical group of Department DISBEF and the biochemical group of Department DISB of the University of Urbino "Carlo Bo" in order to better understand some crucial aspects of brain cancer oncogenesis. Throughout our collaboration we discovered that biochemists are mainly attracted to the instantaneous behaviour of the whole cell, while mathematicians are mostly interested in the evolution along time of small and different parts of it. This collaboration has thus been very challenging. Starting from [23,24,25], we introduce a competitive stochastic model for post-transcriptional regulation of PTEN, including interactions with the miRNA and concurrent genes. Our model also covers protein formation and the backward mechanism going from the protein back to the miRNA. The numerical simulations show that the model reproduces the expected dynamics of normal glial cells. Moreover, the introduction of translational and transcriptional delays offers some interesting insights for the PTEN low expression as observed in brain tumor cells.

MeSH terms

  • Algorithms
  • Brain Neoplasms / metabolism*
  • Computer Simulation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / metabolism
  • Models, Biological
  • Models, Statistical
  • Neuroglia / metabolism
  • PTEN Phosphohydrolase / metabolism*
  • Poisson Distribution
  • Probability
  • RNA Processing, Post-Transcriptional
  • Stochastic Processes

Substances

  • MicroRNAs
  • PTEN Phosphohydrolase
  • PTEN protein, human