Mathematical modelling of Her2 (ErbB2) PI3K/AKT signalling pathways during breast carcinogenesis to include PTPD2

ErbB2 overexpression plays an important pathogenic role in breast cancer and acts via phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathways. Mathematical models for the PI3K/AKT signalling pathways have been derived but have not incorporated a newly defined positive regulator of the ErbB2 signalling network, phosphatidic acid-protein-tyrosine phosphatase D2 (PTPD2). We hypothesize that PTPD2 acts on the AKT signalling pathway by binding PA to PTPD2 and participates in AKT phosphorylation through PIP3. Based on this, a new mathematical model of ErbB2/P13K/AKT and PLD2/PTPD2 pathways was derived using 22 ordinary differential equations. The derived simulation results were consistent with the experimental results. This model is used to study the change of ppAKT concentration with time at different initial concentrations of PDPD2, PLD2, PI3K and PTEN in the signal pathway. Taken together, these observations suggest therapeutic approaches for erbb2-positive breast cancer which is resistant to ErbB2 targeted therapy based on inhibitors for PI3K, PTPD2 or PLD2.